Modified oligonucleotide and its preparation and application

ABSTRACT

The present invention relates to a modified oligonucleotide, its preparation and application. The invention eables stabilizing the oligonucleotide by introducing a relatively small amount of modified nucleotide at specific UA/UA and/or CA/UG and/or UG/CA site of the oligonucleotide, therefore to decrease the modification-related cytotoxicity and compromising effects on the biological activity.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is the U.S. national phase of International Application No. PCT/CN2010/000405, filed Mar. 30, 2010, which claims the benefit of Chinese Patent Application No. 200910081145.8, filed Apr. 3, 2009 and Chinese Patent Application No. 200910081144.3, filed Apr. 3, 2009.

FIELD OF THE INVENTION

This invention relates to nucleic acid technology, specifically to modified oligonucleotide and its preparation, its application in RNA interference, pharmaceutical compositions, and disease treatment.

BACKGROUND OF THE INVENTION

RNA interference (RNAi) is a gene silencing phenomenon mediated by double-stranded RNA (dsRNA) molecules, shutting down homologous gene expression at mRNA level. RNAi is a post-transcriptional gene regulation mechanism, also named post-transcriptional gene silencing (PTGS), target gene knockdown, or gene silencing.

RNAi phenomenon was first reported in plants by two different research groups in 1990. Later on, this phenomenon was further observed in almost all eukaryotes, including C. elegans, Drosophila, zebrafish and mice.

In 1999, RNA fragments of 21 to 25 nucleotides in length were identified in plant RNAi by Hamilton and Baulcombe. These small RNA fragments were demonstrated to be the mediator necessary for RNAi, and thus named as small interfering RNA (siRNA).

Double-stranded siRNA conjugates with endogenous enzymes and proteins, and then forms RNA-induced silencing complex (RISC). In the process of RNAi, while the sense RNA strand of double-stranded siRNA is excluded from the complex, the antisense RNA strand functions to guide RISC to target mRNA at homologous locus, resulting in the degradation of target mRNA and gene silencing mediated by RNase III component within RISC complex.

However, due to the vulnerability of siRNA to serum ribonuclease that resulting in serum instability, synthetic siRNAs are often chemically modified so as to increase their serum stability and gene silencing activity.

Even though, in consideration of the poor understanding of the degradation process and mechanism of RNAi, random modification strategy is performed to stabilize siRNA in body fluids. Although this strategy can improve serum stability of the modified siRNAs to some extent, it usually ends up with excessive chemical modifications and results in increased cytotoxicity and compromised biological activity in many cases, due to the lack of theoretical guidance. This therefore restricts the in vivo applications of the modified siRNAs. In addition, the extensive siRNA modification strategy also limits the use of many chemical modifications that have great stabilizing effect, however with relatively high cytotoxicity.

Therefore, there is an urgent need to develop a specific modification strategy for synthetic siRNAs, to achieve optimum serum stability with minimal chemical modifications.

SUMMARY OF THE INVENTION

The present invention is to overcome technical problem caused by the extensive siRNA modification commonly performed in the art, by providing a kind of modified oligonucleotide. The oligonucleotides provided in the present invention include, without limitation, RNA and DNA oligonucleotides, also include a variety of chemically modified nucleic acid derivatives including single-stranded and double-stranded nucleic acid molecules. That is, the modified oligonucleotides disclosed in the invention include but do not limit to single-stranded RNA molecules (ssRNA), single-stranded DNA molecule (ssDNA), double-stranded RNA molecules (dsRNA), double-stranded DNA molecule (dsDNA), as well as a variety of nucleic acid derivatives modified from the above molecules. Preferably, the oligonucleotides are double-stranded RNA molecules (dsRNA); more preferably, the oligonucleotides are small interfering nucleic acids (siRNA).

To address these problems, the present invention discloses a modified oligonucleotide comprising a first nucleic acid fragment and a second nucleic acid fragment. Said first nucleic acid fragment and second nucleic acid fragment can form double-stranded region, wherein the modified oligonucleotide has at least one of the following modifications, the modification(s) improve the stability of the modified oligonucleotide in mammalian body fluids:

-   -   (a) The first nucleic acid fragment contains at least one         contiguous UA sequence, the second nucleic acid fragment         contains at least one contiguous UA sequence complementary to         the UA sequence in the first nucleic acid fragment. The UA         sequence(s) of the first nucleic acid fragment and the         complementary UA sequence(s) of the second nucleic acid fragment         pair to form UA/UA site(s); wherein at least one of the         nucleotides in at least one of the UA/UA site(s) is a modified         nucleotide;     -   (b) The first nucleic acid fragment contains at least one         contiguous CA or UG sequence, the second nucleic acid fragment         contains at least one contiguous CA or UG sequence complementary         to the CA or UG sequence in the first nucleic acid fragment, the         CA or UG sequence(s) of the first nucleic acid fragment and the         CA or UG sequence(s) of the second nucleic acid fragment pair to         form CA/UG and/or UG/CA site(s); wherein at least one of the         nucleotides in at least one of the CA/UG and/or UG/CA site(s) is         a modified nucleotide;     -   (c) The first nucleic acid fragment contains at least one         contiguous UA sequence and at least one contiguous CA or UG         sequence, the second nucleic acid fragment contains at least one         contiguous UA sequence complementary to the UA sequence of the         first nucleic acid fragment and one contiguous CA or UG sequence         complementary to the CA or UG sequence of the first nucleic acid         fragment, the UA sequence(s) of the first nucleic acid fragment         and the UA sequence(s) of the second nucleic acid fragment pair         to form UA/UA site(s), the CA or UG sequence(s) of the first         nucleic acid fragment and the UG or CA sequence(s) of the second         nucleic acid fragment pair to form CA/UG or UG/CA site(s);         wherein at least one of the nucleotides in at least one of the         UA/UA site(s) is a modified nucleotide, and at least one of the         nucleotides in at least one of the CA/UG or UG/CA site(s) is a         modified nucleotide.

According to the present invention, in the cases that the first nucleic acid fragment contains at least one contiguous UA sequence, the second nucleic acid fragment contains at least one contiguous UA sequence complementary to the UA sequence in the first nucleic acid fragment, the UA sequence(s) of the first nucleic acid fragment and the complementary UA sequence(s) of the second nucleic acid fragment pair to form UA/UA site(s), modification can be made for at least one of the nucleotides in one UA/UA site, modification can also be made for at least one of the nucleotides in multiple UA/UA sites, modifications can also be made for multiple nucleotides in multiple UA/US sites. Preferably, only one uracil nucleotide is modified in each UA/UA site.

In the cases that first nucleic acid fragment contains at least one contiguous CA or UG sequence, the second nucleic acid fragment contains at least one contiguous CA or UG sequence complementary to the CA or UG sequence in the first nucleic acid fragment, the CA or UG sequence(s) of the first nucleic acid fragment and the CA or UG sequence(s) of the second nucleic acid fragment pair to form CA/UG and/or UG/CA site(s), modification can be made for at least one of the nucleotides in one CA/UG or UG/CA site, modification can also be made for at least one of the nucleotides in multiple CA/UG or UG/CA site(s), furthermore, modifications can also be made for multiple nucleotides in multiple CA/UG or UG/CA sites. Preferably, only one cytosine nucleotide is modified in each CA/UG or UG/CA site.

In the cases that the first nucleic acid fragment contains at least one contiguous UA sequence and at least one contiguous CA or UG sequence, the second nucleic acid fragment contains at least one contiguous UA sequence complementary to the UA sequence of the first nucleic acid fragment and one contiguous CA or UG sequence complementary to the CA or UG sequence of the first nucleic acid fragment, the UA sequence(s) of the first nucleic acid fragment and the UA sequence(s) of the second nucleic acid fragment pair to form UA/UA site(s), the CA or UG sequence(s) of the first nucleic acid fragment and the UG or CA sequence(s) of the second nucleic acid fragment pair to form CA/UG or UG/CA site(s), modification can be made for at least one of the nucleotides in UA/UA and CA/UG or UG/CA site; modification can also be made for at least one of the nucleotides in at least one of the UA/UA sites, at the same time, modification is also made for at least one of the nucleotides in at least one of the CA/UG or UG/CA sites.

In the present invention, the term “first nucleic acid fragment” refers to a nucleic acid fragment partly or completely homologous to the coding region of a target gene, the term “second nucleic acid fragment” refers to a nucleic acid fragment complementary to the coding region of a target gene. The term “complementary” refers to that two nucleotides can pair with each other in hybridization condition. For example, adenine (A) can pair with thymine (T) or uracil (U), cytosine (C) can pair with guanine (G).

In the present invention, said oligonucleotides can be small interfering RNA (siRNA) against a variety of target genes. For example, target genes can be an endogenous gene to be studied, a gene whose expression to be inhibited; for example, a gene associated with a disease or a disorder, such as oncogenes, viral genes, cell surface receptors, nuclear receptors, or genes implicated in cellular signaling pathway.

Based on the sequence of a target gene, specific siRNAs can be designed by person having ordinary skill in the art to which this invention belongs. For example, input target gene sequences or their NCBI Genbank sequence number into various siRNA design softwares, such as Insert Design Tool for the shRNA Vectors (Ambion), shRNA Explorer (Gene Link), siDirect (Yuki Naito et al. University of Tokyo), SiRNA at Whitehead (Whitehead Institute for Biomedical Research), BLOCK-iT RNAi Designer (invitrogen), RNAi Design (IDT), RNAi Explorer (Gene Link), siRNA Target Finder (Ambion), or siSearch (Stockholm Bioinformatics Center) etc., the software can design gene-specific siRNAs according to the requirements and siRNA design principles.

In addition, several siRNA design software can also perform genome-wide or transcriptome-wide homology search, so as to obtain target gene-specific or sequence-specific siRNAs. Said siRNA design software and principles are commonly understood by person having ordinary skill in the art to which this invention belongs. All these information are therefore included in the present invention as references.

In a preferred embodiment, the invention relates to a modified oligonucleotide, wherein all the nucleotides are unmodified nucleotides except the nucleotides in said CA/UG and/or UA/UA and/or UG/CA site(s). In these cases, incorporation of minimal chemical modifications into the modified oligonucleotide not only increase its stability, maintain its biological activity, further reduces potential cytocoxicity caused by extensive chemical modifications.

In the present invention, the modified oligonucleotide can be single-stranded or double-stranded oligonucleotide. In the cases of single-stranded oligonucleotide, said first nucleic acid fragment and second nucleic acid fragment can form double-stranded region by base-pairing of their complementary sequences. In the cases of double-stranded oligonucleotide, said modified oligonucleotide can contain a sense strand and antisense strand. The sense strand can be a contiguous fragment, or several discontiguous fragments; the antisense strand is a contiguous fragment.

In one aspect of the present invention, the invention relates to a modified oligonucleotide comprising a sense strand and an antisense chain. Said sense strand and antisense strand are contiguous nucleic acid fragments, said first nucleic acid fragment is in the sense strand, and said second nucleic acid fragment is in the antisense strand.

In another aspect of the present invention, the invention relates to a modified oligonucleotide comprising a sense strand and an antisense strand. Said sense strand comprises two or more discontiguous sense-strand fragments, said antisense strand is a contiguous nucleic acid fragment. Said first nucleic acid fragment is in the one or more sense-strand fragments, and the second nucleic acid fragment is in the antisense strand.

In the present invention, the term “sense strand” refers to a nucleic acid fragment partly or completely homologous to the coding region of a target gene, in the cases that the modified oligonucleotide is a double-stranded molecule. The term “second nucleic acid fragment” refers to a nucleic acid fragment complementary to the coding region of a target gene, in the cases that the modified oligonucleotide is a double-stranded molecule. In addition, in the cases that said modified oligonucleotide is a double-stranded molecule, said sense strand and antisense strand are contiguous nucleic acid fragments, the term “sense strand” and the term “first nucleic acid fragment” are used interchangeably, the term “antisense strand” and the “second nucleic acid fragment” are used interchangeably.

In the present invention, the term “sense-strand fragment” refers to the component fragments of the sense strand, in the cases that said sense strand comprises discontiguous fragments; the total length of all sense-strand fragments is equal to length of the sense strand. In addition, in the cases that said sense strand contains UA/UA site(s), the term “sense-strand fragment” and “first nucleic acid fragment” are used interchangeably.

In the present invention, said modified oligonucleotide can comprise only ribonucleotides, can also be a hybrid molecule comprising ribonucleotides and at least one deoxyribonucleotide.

In present invention, the term “potential toxicity” refers to the cellular toxicity effects caused by involved chemical modification(s) made on the modified nucleotide(s). In another word, it refers to the inhibition effects on cell growth, and thus named as “growth inhibition ratio” throughout this invention. The higher the growth inhibition ratio is, the greater the potential cytotoxicity is.

In the invention, said modifications are commonly understood by person having ordinary skill in the art to which this invention belongs. For example, the modification(s) are one or a combination of the following modifications:

(a) modifying the phosphodiester bond(s) connecting nucleotides in the oligonucleotide;

(b) modifying the sugar(s) of the nucleotide in the oligonucleotide;

(c) modifying the base(s) of the nucleotide in the oligonucleotide.

Said modification of phosphodiester bond is made by modifying the oxygen of the phosphodiester bond, including phosphorothioate modification and boranophosphate modification. As shown in the figures, these modifications replace the oxygen of the phosphodiester bond by sulfur or boron, respectively. Both modifications can stabilize the structure of siRNA, maintain high specificity and affinity of base pairing. However, boranophosphate siRNAs have stronger hydrophobicity and readily to form protein conjugate in the plasma, and less toxic to human body than phosphorothioate siRNAs.

Said modification of ribose refers to modifications of hydroxyl at 2′-position of the pentose sugars in siRNAs. Replacing the 2′-OH by methoxy or fluorine interfers with the interaction between the modified siRNA and serum ribonuclease, render the siRNA more stable in serum, and increase its resistance to nuclease degradation. Modifications of the 2′-hydroxyl of the pentose sugars comprises 2′-deoxy-2′-fluoro modification (2′-F), 2′-O-methyl modification (2′-OME), 2′-methoxyethyl-modification (2′-MOE), 2,4′-dinitrophenol-modification (2′-DNP), locked nucleic acid (LNA), 2′-amino modification (Amina modification), 2′-deoxy modification, etc.

Said base modification refers to modifications of the base of the nucleotide, including commonly used modifications such as 5′-bromo-uracil and 5′-iodo-uracil, and other modifications such as N3-methyl-uracil and 2,6-diaminopurine, and so on.

Preferably, modified oligonucleotide provided in the present invention is a 2′-modified nucleotide. More preferably, the modified nucleotide is a 2′-OMe-modified or 2′-Fluoro-modified nucleotide. These modifications are made to increase the stability of the modified oligonucleotides in mammalian body fluids and enhance their resistance to nuclease degradation.

The present invention also relates to a method for preparing said modified oligonucleotide, comprising the steps of: selecting UA/UA and/or CA/UG site(s) from the oligonucleotide sequence to be prepared, synthesizing the oligonucleotide, wherein replacing nucleotide(s) in the selected site(s) by corresponding modified nucleotide(s). The resulting oligonucleotide comprises a first nucleic acid fragment and a second nucleic acid fragment, the first nucleic acid fragment and the second nucleic acid fragment form double-stranded region. (a) said first nucleic acid fragment contains at least one contiguous UA sequence, the second nucleic acid fragment contains at least one contiguous UA sequence complementary to the UA sequence in the first nucleic acid fragment, the UA sequence(s) of the first nucleic acid fragment and the complementary UA sequence(s) of the second nucleic acid fragment pair to form UA/UA site(s), wherein at least one of the nucleotides in said UA/UA site(s) is a modified nucleotide; more preferably, only one uracil nucleotide in each UA/UA site is a modified nucleotide.

-   -   (b) The first nucleic acid fragment contains at least one         contiguous CA or UG sequence, the second nucleic acid fragment         contains at least one contiguous CA or UG sequence complementary         to the CA or UG sequence in the first nucleic acid fragment, the         CA or UG sequence(s) of the first nucleic acid fragment and the         CA or UG sequence(s) of the second nucleic acid fragment pair to         form CA/UG and/or UG/CA site(s), wherein at least one of the         nucleotides in said CA/UG and/or UG/CA site(s) is a modified         nucleotide; more preferably, only cytosine nucleotide(s) in         CA/UG or UG/CA site(s) is/are modified nucleotide(s).     -   (c) The first nucleic acid fragment contains at least one         contiguous UA sequence and at least one contiguous CA or UG         sequence, the second nucleic acid fragment contains at least one         contiguous UA sequence complementary to the UA sequence of the         first nucleic acid fragment and at least one contiguous CA or UG         sequence complementary to the CA or UG sequence of the first         nucleic acid fragment, the UA sequence(s) of the first nucleic         acid fragment and the UA sequence(s) of the second nucleic acid         fragment pair to form UA/UA site(s), the CA or UG sequence(s) of         the first nucleic acid fragment and the UG or CA sequence(s) of         the second nucleic acid fragment pair to form CA/UG or UG/CA         site(s); wherein at least one of the nucleotides in said UA/UA         and CA/UG and/or UG/CA site(s) is a modified nucleotide; or, at         least one of the nucleotides in said UA/UA site is a modified         nucleotide, and at the same time, at least one of the         nucleotides in said CA/UG and/or UG/CA site(s) is a modified         nucleotide.

In a preferred embodiment, the present invention relates to a modified oligonucleotide prepared by the claimed method in the invention, wherein all the nucleotides are unmodified nucleotides except the nucleotides in said UA/UA and/or CA/UG and/or UG/CA site(s).

In the invention, the structures of said oligonucleotides prepared by the provided method are commonly understood by person having ordinary skill in the art to which this invention belongs. Said structures can be any structure of existing nucleotide or oligonucleotide.

For example, the invention relates to a modified oligonucleotide that is prepared by the claimed method in the present invention can be a hairpin-structured and single-stranded nucleic acid molecule, the complementary nucleic acid sequences of the first nucleic acid fragment and the second nucleic acid fragment pair to form double-stranded region. In another aspect, the invention relates to a modified oligonucleotide that is prepared by the claimed method in the invention can contain a sense strand and an antisense strand, the sense strand and the antisense strand are contiguous nucleic acid fragments. Said first nucleic acid fragment is in the sense strand, said second nucleic acid fragment is in the antisense strand.

In yet another aspect, the invention relates to a modified oligonucleotide that is prepared by the claimed method in the present invention can contain a sense strand and an antisense strand. The sense strand contains two or more discontiguous sense-strand component fragments, the antisense strand is a contiguous nucleic acid fragment. Said first nucleic acid fragment is in one or more sense-strand component fragments, the second nucleic acid fragment is in the antisense strand.

In yet another aspect, the invention relates to a modified oligonucleotide that is prepared by the claimed method in the present invention can be a hybrid nucleic acid molecule comprising ribonucleotides and at least one deoxyribonucleotide.

In general, the oligonucleotides of the present invention can be synthesized using conventional protocols known in the art. Alternatively, synthesis can be performed by specialized biotechnology companies providing oligonucleotide synthesis service, such as Shanghai GenePharma Ltd, Guangzhou Ribo Biotechnology Ltd, or Invitrogen Ltd.

In general, the procedure of oligonucleotide synthesis comprises the steps of: (a) Synthesis of oligonucleotide; (b) Deprotection; (c) Purification; and (d) Desalination.

For example, detailed procedure of synthesizing a siRNA comprises the steps of:

-   -   (a) Synthesis of oligonucleotide. Single-stranded RNA         oligonucleotide is produced by solid phase synthesis on a scale         of 1 mmol, using an automatic DNA/RNA synthesizer (for example,         Applied Biosystems EXPEDITE8909). Coupling time is set to 10-15         minutes for each synthesis cycle. From the starting material of         5′-O-dimethoxy-thymidine solid support, the first nucleotide is         connected to the support in the first synthesis cycle; and for         each following synthesis cycle, a new nucleotide is connected to         the product of cycle n−1. Repeat the synthesis cycle until the         completion of the synthesis of the oligonucleotide.     -   (b) Deprotection. Move siRNA-conjugated solid support into a         test tube, and add 1 ml of ethanol/triethylamine (volume ratio         of 1:3) in the test tube; seal the tube and place it in an         incubator at 55 to 70° C., incubate for 2 to 30 hours; take out         the siRNA-conjugated solid support and wash twice with         double-distilled water (1 ml for each wash); collect the eluate         and dry at room temperature for 30 minutes. Then, add 1 ml of 1M         tetrabutylammonium fluoride in tetrahydrofuran solution, react         at room temperature for 4 to 12 hours; add 2 ml ethanol and         collect the sediment for obtaining the crude product of         synthesized oligonucleotide.     -   (c) Purification. Dissolve the obtained crude oligonucleotide in         2 ml ammonium acetate solution (1 mole/ml), separate the         oligonucleotide using C18 high pressure liquid chromatography         for purified product oligonucleotide.     -   (d) Desalination. To further remove salt from the         oligonucleotide, wash the purified oligonucleotide product 2 to         4 times by ethanol solution (2 ml per wash, 75% in weight         ratio), and dry the oligonucleotide product at room temperature.         Then, dissolve the sense strand and the antisense strand in 1 to         2 ml annealing buffer (10 mM Tris, pH 7.5-8.0, 50 mM NaCl), heat         the solution to 95° C. and let it cool down slowly to room         temperature, and keep the solution at room temperature for 16 to         22 hours for obtaining desalted siRNA solution.

The present invention also relates to a pharmaceutical composition for inhibiting the expression of a target gene in a mammal. Said pharmaceutical composition comprises at least one of the modified oligonucleotides disclosed in the invention, and at least one of pharmaceutically acceptable carriers. As used herein, “pharmaceutically acceptable carrier” should be compatible with the oligonucleotide(s) included in said pharmaceutical composition. In general, the “pharmaceutically acceptable carrier” can blend with the oligonucleotide(s) and do not significantly compromise the inhibition activity of the pharmaceutical composition on gene expression, under normal circumstances.

Examples of the substance of “pharmaceutically acceptable carrier” or components of the “pharmaceutically acceptable carrier” are sugars, such as lactose, glucose and sucrose; starch such as corn starch and potato starch; cellulose and its derivatives such as carboxymethyl fiber sodium, ethyl cellulose and methyl cellulose; West tragacanth powder; malt; gelatin; talc; solid lubricant such as stearic acid and magnesium stearate; calcium sulfate; vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and cocoa butter; polyols such as propylene glycol, glycerol, sorbitol, mannose alcohol and polyethylene glycol; alginate; emulsifiers such as Tween; wetting agents, such as lauryl sulfate sodium; colorants; flavoring agent; pressure tablets, stabilizers; antioxidants; preservatives; pyrogen-free water; isotonic salt solution; and phosphate buffer, etc. Preferably, the carriers are selected from saline, glycerol and phosphate phosphate buffer saline.

The pharmaceutical composition provided by the invention can be made in a variety of medically acceptable formulations, and administrated by physicians in an optimal dosage according to patient's type, age, weight, disease condition, delivery approach and other factors. The formulations provided by the present invention includes a variety of liquid formulations such as oral, injection, sublingual agent, tablet formulations prepared by adding suitable excipient, capsule formulation, or a variety of other formulations, etc. Preferred formulations of said pharmaceutical composition comprise injection, capsules, sublingual, oral liquid, aerosol, or patch.

In another aspect, the invention also provides a method for preparing the pharmaceutical composition, said method comprises formulating the modified oligonucleotides and pharmaceutically acceptable carriers to obtain the said pharmaceutical compositions. No particular order or rules need to be applied to the mixing of the modified oligonucleotides and the pharmaceutically acceptable carriers.

In another aspect, the invention also relates to a method for inhibiting the expression of a target gene in a cell, compreseing:

-   -   (a) introducing the modified oligonucleotide(s) into at least         one of the cells; and     -   (b) incubating the cells for a time sufficient to obtain         inhibition of the expression of the target gene in the cell.

Preferably, the cells are mammalian cells.

The present invention also relates to a method for preparing an oligonucleotide that is highly stable in a biological sample and can inhibite the expression of a target gene, comprising the steps of:

(a) selecting one or more nucleic acid sequences of 18 to 30 nucleotides in length from the nucleotide sequence of the mRNA resulting from the transcription of the target gene; and

(b) synthesizing the selected sequences, wherein one strand comprises a sequence complementary to selected sequence in (a); and

(c) testing one or more oligonucleotides of (b) for their activity to inhibit the expression of the target gene in a biological sample; and

(d) selecting one or more oligonucleotides of (c) possessing the activity to inhibit the expression of the target gene in a biological sample; and

(e) in the oligonucleotides selected in (d), identifying in the nucleotide sequences of all occurrences of the UA/UA, CA/UG and UG/CA site(s); and

(f) synthesizing one or more oligonucleotides selected in (d), wherein at least one nucleotide in the UA/UA, CA/UG and UG/CA site(s) identified in (e) is replaced by its corresponding modified nucleotide.

Preferably, only cytidine nucleotide(s) in all occurrences of the CA/UG or UG/CA site is/are modified, only one uracil nucleotide in each UA/UA site is modified; more preferably, all the nucleotides are unmodified nucleotides except the nucleotides in said CA/UG and/or UA/UA and/or UG/CA site(s).

A method of treating a disease caused by expression of a target gene in a subject is provided in the present invention. Said method comprises administering to said subject a pharmaceutical composition comprising at least one of said oligonucleotides and a pharmaceutically acceptable carrier. Preferably, the subject is mammalian; more preferably, the subject is human being.

The present invention also relates to a method for preparing an oligonucleotide with nuclease resistance, said method comprises the steps of:

-   -   (a) identifying in the nucleotide sequence of the         oligonucleotide all occurrences of UA/UA, CA/UG and UG/CA         site(s); and     -   (b) synthesizing the oligonucleotide, wherein replaces         nucleotide(s) in the UA/UA, CA/UG and UG/CA site(s) identified         in (a) by corresponding modified nucleotide(s). Preferably, only         cytidine nucleotide(s) in all occurrences of the CA/UG or UG/CA         site(s) identified in (a) is/are modified, only one uracil         nucleotide in each UA/UA site identified in (a) is modified.         More preferably, all the nucleotides are unmodified nucleotides         except the nucleotides in said CA/UG and/or UA/UA and/or UG/CA         site(s).

The invention also relates to a method to identify an oligonucleotide with stability in biological samples, comprising the steps of:

-   -   (a) providing a first modified oligonucleotide, and a second         oligonucleotide identical in sequence to the first         oligonucleotide except that it dose not have modified         nucleotide(s); and     -   (b) determining the stability and the degradation process of         said first and second oligonucleotide in the biological sample         by contacting the two oligonucleotides with the biological         sample under identical conditions,         Whereby, where the first modified oligonucleotide is degraded         less rapidly than the second oligonucleotide, the         oligonucleotide with stability in a biological sample is         identified.

By specifically modifying the UA/UA and/or CA/UG and/or UG/CA site(s) identified in an oligonucleotid, the invention achieves stabilizing the modified oligonucleotide by introducing only a relatively small amount chemically modified nucleotides into the oligonucleotide. Compared to randomly modified oligonucleotide in the art, the specific modification approach disclosed in the present invention greatly reduces the potential cytotoxicity and influence on the biological activity of the modified oligonucleotide.

Inventors of the present invention performed comprehensive investigation on the in vivo degradation of synthetic oligonucleotide, and found that replacing a relatively small amount of the nucleotides in UA/UA and/or CA/UG site(s) identified in a oligonucleotide sequence by corresponding chemically modified nucleotide(s) can greatly increase the stability of the modified oligonucleotide in biological samples, and at the same time, reduces the cytotoxicity caused by extensive and random modifications usually performed in the art, as well as the effects on biological activity.

The present invention is further illustrated using the following embodiments. Should be understood that the materials, methods, and examples described in the present invention are illustrative only and not intented to be limiting. Unless otherwise defined, all reagents and culture medium used in the invention are commercially available.

EXAMPLE 1 Synthesis of siRNA Oligonucleotides

siRNA oligonucleotides against target genes in table 1-182 were synthesized by Genepharma Ltd (Shanghai, China).

EXAMPLE 2 Assays of Serum Stability, Silencing Efficacy and Cytotoxicity of Variously Modified siRNA

Serum stability, silencing efficacy and cytotoxicity assay of modified and unmodified siRNAs in table 1-182 were tested using the methods of:

1. Serum Stability Assay

Serum degradation assays were performed at 37° C. by incubating 4 μL 20 μM modified or unmodified siRNA in 32 μL 1×PBS solution, containing 4 μL fetal bovine serum (Sigma). The final serum concentration was 10%. After serum treatment of 0, 3 or 6 hours, 10 μL reaction solution was removed and frozen immediately in liquid nitrogen to terminate the reaction. The samples were then stored at −80° C. until analysis.

Prepare a 20% polyacrylamide gel; mix 3 uL 3× loading buffer (30 mM EDTA, 36% glycerol, 0.06% bromophenol blue) with serum-treated siRNA sample; then load the sample into the gel and run electrophoresis at 80 mA under constant current condition. After electrophoresis, add 1× Sybr Gold (Invitrogen, Cat. 11494) into the sample and let it stain for 10 minutes before imaging and analysis. The results were presented in Table 1-182.

2. Silencing Efficacy Assay

Human embryonic kidney cells (HEK293) were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mM L-glutamine, 100 units/ml penicillin and 100 μg/ml streptomycin (Life Technologies, Gibco), and seeded into 24-well plates at a density of 1×10⁵ cells (0.5 mL culture medium/well). After 24 hours incubation and the cell density reached 50% confluence, the culture medium was changed to Opti-MEM (Gibco). Lipofectamine™ 2000 transfection reagent (Invitrogen) was used to co-transfect siRNA and reporter plasmids. Report vector (0.17 μg/well) carrying the target site of tested siRNA and firefly luciferase gene was transfected into the cells together with pRL-TK control vector carrying renilla luciferase gene. The final concentration of siRNA was 13 nM. Each siRNA was parallely transfected in three wells, with the same amount of the two reporter plasmids. The three wells without siRNA treatment were used as control. Four hours after transfection, the culture medium was changed to one milliliter DMEM growth medium (10% fetal bovine serum, 2 mM L-glutamine, 100 units/ml penicillin and 100 μg/ml streptomycin). Twenty-four later, the cells were lysated by adding 10 uL cell lysis buffer, and the activity of both luciferases was measured with a fluorometer (Synergy HT, BioTek, USA), using Dual-Luciferase reporter assay system (Promega) according to the manufacturer's instructions. Silencing efficacy of the siRNA was calculated by the following formula, using siRNA-untreated cells as control. All the experiments were performed in triplicate and repeated for at least twice. The results were shown in table 1-182. Silencing efficacy=(the expressional amount of firefly luciferase in test group/the expressional amount of renilla luciferase in test group)/(the expressional amount of firefly luciferase in control group/the expressional amount of renilla luciferase in control group)

3. Cytotoxicity Assay of Modified siRNA

Human embryonic kidney cells (HEK293) were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mM L-glutamine, 100 units/ml penicillin and 100 μg/ml streptomycin (Life Technologies, Gibco), and seeded into 24-well plates at a density of 1×10⁵ cells (0.5 mL culture medium/well). After 24 hours incubation and the cell density reached 50% confluence, the culture medium was changed to Opti-MEM (Gibco). Lipofectamine™ 2000 transfection reagent (Invitrogen) was used to transfect chemically synthetic siRNA into the cells at a final concentration of 13 nM. Each siRNA was parallely transfected in three independent wells, with three other siRNA-untreated wells as control. Four hours after transfection, the culture medium was changed to one milliliter DMEM growth medium (10% fetal bovine serum, 2 mM L-glutamine, 100 units/ml penicillin and 100 μg/ml streptomycin).

Twenty-four later, removed the culture medium and washed the cells once with PBS. Add 1 mL PBS and 10 μL MTT into each well, incubate in a 5% CO₂ incubator at 37° C. for 4-6 hours; add 0.1 mL acidified isopropanol into each well, mix by vortexing; measure the absorbance value (A value) at 570 nm for each well, using a microplate reader. The growth inhibition ratio was calculated using the following formula, the results were shown in table 1-182. Growth inhibition ratio (%)=(A value of test group−A value of control group)/A value of control group×100%

TABLE 1 Human KAZRIN(NM_201628) 718-738 BP (SEQ ID NO: 1) Locus Expression Growth Gene siRNA Stability inhibition ratio inhibition ratio 1-1 Unmodified siRNA + 84%  0% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 2) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 3) 1-2A Random modification (2′-deoxy-2′-fluoro) ++ 27% 37% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 4) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 3) 1-2B Random modification (2′-O-methyl) ++  0% 32% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 2) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 5) 1-3A Specific modification (2′-O-methyl) ++ 27% 15% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 6) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 7) 1-3B Specific modification (2′-deoxy-2′fluoro) +++ 44% 12% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 8) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 7) 1-3C Specific modification (2′-O-methyl) ++ 56% 10% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 6) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 9) 1-3D Specific modification (2′-O-methyl) ++ 81% 11% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 8) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 9) 1-3E Specific modification (2′-O-methyl) +++ 49% 10% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 8) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 10) 1-3F Specific modification (2′-deoxy-2′-fluoro) ++ 49% 14% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 2) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 7) 1-3G Specific modification (2′-deoxy-2′-fluoro) ++ 85%  0% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 8) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 3) 1-3H Specific modification (2′-O-methyl) ++ 84%  6% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 2) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 9) 1-3I Specific modification (2′-O-methyl) ++ 23% 10% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 6) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 10) 1-3J Specific modification (2′-O-methyl) ++ 41% 14% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 11) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 7) 1-3K Specific modification (2′-deoxy-2′-fluoro) ++ 47% 15% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 11) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 10) 1-3L Specific modification (2′-O-methyl) ++ 83% 12% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 11) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 9) 1-3M Specific modification (2′-O-methyl) ++ 59%  7% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 6) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 3) 1-3N Specific modification (2′-deoxy-2′-fluoro) ++ 49%  0% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 2) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 10) 1-3O Specific modification (2′-O-methyl) ++ 85%  5% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 11) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 3) 1-3P Unmodified siRNA(hairpin, unmodified) +++ 85%  0% 5-AGCGCUUAAAGGGCGAGAAGAUUN (SEQ ID NO: 1349) UUUCGCGAAUUUCCCGCUCUUCUNNN (SEQ ID NO: 1350) 1-3Q Specific modification (hairpin, 2′-O-methyl) +++ 53% 10% (SEQ ID NO: 13) 5-AGCGCUUAAAGGGCGAGAAGAUUN (SEQ ID NO: 1349) UUUCGCGAAUUUCCCGCUCUUCUNNN (SEQ ID NO: 1350) 1-3R Specific modification (discontiguous sense strand, +++ 78%  2% 2′-deoxy-2′-fluoro) 5-AGCGCUUAAAGG|GCGAGAAGAUU (SEQ ID NO: 14, 15) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 3) 1-3S Specific modification (hybrid molecule, 2′-O-methyl) ++ 50%  7% 5-AGCGCUUAAAGGGCG(DA)GAAGAUU (SEQ ID NO: 16) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 10) 1-3T Specific modification (hybrid molecule, ++ 79%  9% 2′-deoxy-2′-fluoro) 5-AGCGCUUAAAGGGCG(DA)GAAGAUU (SEQ ID NO: 17) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 9) 1-3U Specific modification (phosphodiester bond +++ 45% 11% modification) 5-AGCGCUUAAAGGG-CGAGAAGAUU (SEQ ID NO: 18) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 10) 1-3V Specific modification (2′-deoxy-2′-fluoro) +++ 51%  8% 5-AGCGCUUAAAGGGCGAGAAGAUU (SEQ ID NO: 8) UUUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 10)

TABLE 2 Mouse(NM_008960.2) 1148-1166 BP (SEQ ID NO: 19) Locus Expression Growth inhibition Gene SIRNA Stability inhibition ratio ratio 2-1 Unmodified siRNA + 86%  0% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 20) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21) 2-2A Random modification (2′-O-methyl) ++ 15% 34% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 20) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 22) 2-2B Random modification (2′-deoxy-2′-fluoro) ++ 37% 38% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 23) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21) 2-3A Specific modification (2′-deoxy-2′-fluoro) ++ 57% 17% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 24) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 25) 2-3B Specific modification (2′-O-methyl) +++ 24% 34% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 26) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 27) 2-3C Specific modification (2′-O-methyl) +++ 51% 17% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 26) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 25) 2-3D Specific modification (2′-O-methyl) ++ 44% 37% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 28) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 25) 2-3E Specific modification (2′-O-methyl) +++  7% 52% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 23) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 29) 2-3F Specific modification (2′-O-methyl) ++ 81% 14% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 30) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 31) 2-3G Specific modification (2′-O-methyl) +++ 32% 35% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 32) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 31) 2-3H Specific modification (2′-O-methyl) ++ 79%  6% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 24) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21) 2-3I Specific modification (2′-O-methyl) ++ 51% 42% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 23) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21) 2-3J Specific modification (2′-deoxy-2′-fluoro) ++ 75% 16% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 33) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21) 2-3K Specific modification (2′-O-methyl) ++ 84%  4% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 34) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21) 2-3L Specific modification (2′-O-methyl) ++ 81%  3% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 30) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21) 2-3M Specific modification (2′-deoxy-2′-fluoro) +++ 54% 33% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 23) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21) 2-3N Specific modification (2′-O-methyl) +++ 82%  5% 5-AACCCACCACAGCUAGAACUUNN (SEQ ID NO: 35) UUGGGUGGUGUCGAUCUUGAANN (SEQ ID NO: 36) 2-3O Specific modification (2′-deoxy-2′-fluoro) ++ 14% 23% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 20) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 37) 2-3P Unmodified siRNA (hairpin, unmodified) +++ 78%  5% (SEQ ID NO: 38) 5-AACCCACCACAGCUAGAACUUNN (SEQ ID NO: 35) UUGGGUGGUGUCGAUCUUGAANN (SEQ ID NO: 36) 2-3Q Specific modification (hairpin, 2′-O-methyl) +++ 42% 34% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 39) UUGGGUGGUGUCGAUCUUGAA-5 (SEQ ID NO: 21)

TABLE 3 Human BIC(NR_001458.3) 289-310 BP (SEQ ID NO: 40) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 3-1 Unmodified siRNA + 88%  0% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 41) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 42) 3-2A Random modification (2′-O-methyl) ++ 49% 41% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 43) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 42) 3-2B Random modification (2′-deoxy-2′-fluoro) ++ 15% 37% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 41) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 44) 3-3A Specific modification (2′-O-methyl) +++ 80% 11% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 45) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46) 3-3B Specific modification (2′-O-methyl) +++ 51% 31% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 47) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46) 3-3C Specific modification (2′-deoxy-2′-fluoro) +++ 45% 57% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 48) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46) 3-3D Specific modification (2′-deoxy-2′-fluoro) ++ 65% 32% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 49) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46) 3-3E Specific modification (2′-O-methyl) ++ 75% 27% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 50) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46) 3-3F Specific modification (2′-O-methyl) ++ 49% 48% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 43) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46) 3-3G Specific modification (2′-O-methyl) ++ 23% 52% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 1351) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 51) 3-3H Specific modification (2′-O-methyl) ++ 17% 42% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 52) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46) 3-3I Specific modification (2′-deoxy-2′-fluoro) ++ 65% 21% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 50) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 53) 3-3J Specific modification (2′-O-methyl) ++ 17% 51% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 1351) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 54) 3-3K Specific modification (2′-O-methyl) ++ 35% 48% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 1351) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 53) 3-3L Specific modification (2′-deoxy-2′-fluoro) ++ 53% 45% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 43) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 53) 3-3M Specific modification (2′-deoxy-2′-fluoro) ++ 28% 39% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 50) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 55) 3-3N Specific modification (2′-O-methyl) +++  8% 49% 5-UUAAUGCUAAUCGUGAUAGGGGUU (SEQ ID NO: 50) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 44) 3-3O Specific modification (2′-O-methyl) ++ 70%  9% 5-UUAAUGCUAAUCGUGA(DT)AGGGGUU (SEQ ID NO: 56) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46) 3-3P Specific modification (2′-O-methyl) ++ 72% 12% 5-UUAAUGCUAAUCGUGAAGG(DG)GUU (SEQ ID NO: 57) AUAAUUACGAUUAGCACUAUCCCC-5 (SEQ ID NO: 46)

TABLE 4 745-763 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 4-1 unmodified ++ 83% 0% 5-AGAAGGACUACUAACCUCCTT (SEQ ID NO: 58) TTUCUUCCUGAUGAUUGGAGG-5 (SEQ ID NO: 59) 4-2 Random modification (2′-O-methyl) ++ 49% 41%  5-AGAAGGACUACUAACCUCCTT (SEQ ID NO: 60) TTUCUUCCUGAUGAUUGGAGG-5 (SEQ ID NO: 61) 4-3A Specific modification (2′-O-methyl) ++ 80% 15%  5-AGAAGGACUACUAACCUCCTT (SEQ ID NO: 62) TTUCUUCCUGAUGAUUGGAGG-5 (SEQ ID NO: 59) 4-3B Specific modification (2′-O-methyl) +++ 81% 5% 5-AGAAGGACUACUAACCUCCTT (SEQ ID NO: 63) TTUCUUCCUGAUGAUUGGAGG-5 (SEQ ID NO: 64)

TABLE 5 749-767 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 5-1 Unmodified siRNA + 69% 0% 5-GGACUACUAACCUCCAGUUTT (SEQ ID NO: 65) TTCCUGAUGAUUGGAGGUCAA-5 (SEQ ID NO: 66) 5-2 Random modification (2′-O-methyl) ++  7% 53%  5-GGACUACUAACCUCCAGUUTT (SEQ ID NO: 67) TTCCUGAUGAUUGGAGGUCAA-5 (SEQ ID NO: 68) 5-3A Specific modification (2′-O-methyl) ++ 65% 21%  5-GGACUACUAACCUCCAGUUTT (SEQ ID NO: 69) TTCCUGAUGAUUGGAGGUCAA-5 (SEQ ID NO: 66) 5-3B Specific modification (2′-O-methyl) +++ 69% 9% 5-GGAC UAC UAACCUCCAGUUTT (SEQ ID NO: 70) TTCCUGAU GAU UGGAGGUCAA-5 (SEQ ID NO: 71)

TABLE 6 807-825 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 6-1 Unmodified siRNA + 69% 0% 5-GAAACUGGUACUUUCCCCCTT (SEQ ID NO: 72) TTCUUUGACCAUGAAAGGGGG-5 (SEQ ID NO: 73) 6-2 Random modification (2′-deoxy-2′-fluoro) ++ 60% 37%  5-GAAACUGGUACUUUCCCCCTT (SEQ ID NO: 74) TTCUUUGACCAUGAAAGGGGG-5 (SEQ ID NO: 73) 6-3A Specific modification (2′-deoxy-2′-fluoro) ++ 26% 12%  5-GAAACUGGUACUUUCCCCCTT (SEQ ID NO: 76) TTCUUUGACCAU GAAAGGGGG-5 (SEQ ID NO: 75) 6-3B Specific modification (2′-deoxy-2′-fluoro) ++ 58% 8% 5-GAAACUGG UACUUUCCCCCTT (SEQ ID NO: 76) TTCUUUGACCAU GAAAGGGGG-5 (SEQ ID NO: 77)

TABLE 7 818-836 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 7-1 Unmodified siRNA + 70% 0% 5-UUUCCCCCAGGUAACGAUUTT (SEQ ID NO: 78) TTAAAGGGGGUCCAUUGCUAA-5 (SEQ ID NO: 79) 7-2 Random modification (2′-deoxy-2′-fluoro) ++ 68% 21%  5-UUUCCCCCAGGUAACGAUUTT (SEQ ID NO: 80) TTAAAGGGGGUCCAUUGCUAA-5 (SEQ ID NO: 81) 7-3A Specific modification (2′-deoxy-2′-fluoro) ++ 78% 15%  5-UUUCCCCCAGG UA ACGAUUTT (SEQ ID NO: 82) TTAAAGGGGGUCCAUUGCUAA-5 (SEQ ID NO: 79) 7-3B Specific modification (2′-deoxy-2′-fluoro) ++ 75% 8% 5-UUUCCCCCAGG UAACGAUUTT (SEQ ID NO: 83) TTAAAGGGGGUCCAU UGCUAA-5 (SEQ ID NO: 84)

TABLE 8 822-840 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 8-1 Unmodified siRNA + 86% 0% 5-CCCCAGGUAACGAUUUUCUTT (SEQ ID NO: 85) TTGGGGUCCAUUGCUAAAAGA-5 (SEQ ID NO: 86) 8-2 Random modification (2′-O-methyl) ++ 69% 53%  5-CCCCAGGUAACGAUUUUCUTT (SEQ ID NO: 87) TTGGGGUCCAUUGCUAAAAGA-5 (SEQ ID NO: 88) 8-3A Specific modification (2′-O-methyl) ++ 79% 12%  5-CCCCAGGUAACGAUUUUCUTT (SEQ ID NO: 89) TTGGGGUCCAUUGCUAAAAGA-5 (SEQ ID NO: 86) 8-3B Specific modification (2′-O-methyl) ++ 70% 5% 5-CCCCAGG UAACGAUUUUCUTT (SEQ ID NO: 90) TTGGGGUCCAU UGCUAAAAGA-5 (SEQ ID NO: 91)

TABLE 9 889-907 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 9-1 Unmodified siRNA + 57% 0% 5-GGGAAACUGAAAGGCUAUGTT (SEQ ID NO: 92) TTCCCUUUGACUUUCCGAUAC-5 (SEQ ID NO: 93) 9-2 Random modification (2′-deoxy-2′-fluoro) +  6% 47%  5-GGGAAACUGAAAGGCUAUGTT (SEQ ID NO: 92) TTCCCUUUGACUUUCCGAUAC-5 (SEQ ID NO: 94) 9-3A Specific modification (2′-deoxy-2′-fluoro) ++ 51% 14%  5-GGGAAACUGAAAGGC UA UGTT (SEQ ID NO: 95) TTCCCUUUGACUUUCCGAUAC-5 (SEQ ID NO: 93) 9-3B Specific modification (2′-deoxy-2′-fluoro) ++ 50% 4% 5-GGGAAACUGAAAGGC UAUGTT (SEQ ID NO: 96) TTCCCUUUGACUUUCCGAUAC-5 (SEQ ID NO: 93)

TABLE 10 1084-1102 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 10-1 Unmodified siRNA + 97% 0% 5-GCGAGCAGAGAAUCUACCUTT (SEQ ID NO: 97) TTCGCUCGUCUCUUAGAUGGA-5 (SEQ ID NO: 98) 10-2 Random modification (2′-O-methyl) ++ 65% 41%  5-GCGAGCAGAGAAUCUACCUTT (SEQ ID NO: 99) TTCGCUCGUCUCUUAGAUGGA-5 (SEQ ID NO: 98) 10-3A Specific modification (2′-O-methyl) ++ 90% 9% 5-GCGAGCAGAGAAUC UACCUTT (SEQ ID NO: 100) TTCGCUCGUCUCUUAGAU GGA-5 (SEQ ID NO: 101) 10-3B Specific modification (2′-O-methyl) ++ 90% 5% 5-GCGAGCAGAGAAUC UACCUTT (SEQ ID NO: 102) TTCGCUCGUCUCUUAGAU GGA-5 (SEQ ID NO: 103)

TABLE 11 1088-1106 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 11-1 Unmodified siRNA + 79% 0% 5-GCAGAGAAUCUACCUUUCCTT (SEQ ID NO: 104) TTCGUCUCUUAGAUGGAAAGG-5 (SEQ ID NO: 105) 11-2 Random modification (2′-O-methyl) ++ 13% 38%  5-GCAGAGAAUCUACCUUUCCTT (SEQ ID NO: 106) TTCGUCUCUUAGAUGGAAAGG-5 (SEQ ID NO: 107) 11-3A Specific modification (2′-O-methyl) +++ 65% 12%  5-GCAGAGAAUCUACCUUUCCTT (SEQ ID NO: 108) TTCGUCUCUUAGAUGGAAAGG-5 (SEQ ID NO: 105) 11-3B Specific modification (2′-O-methyl) ++ 75% 5% 5-G CAGAGAAUC UACCUUUCCTT (SEQ ID NO: 109) TTCGU CUCUUAGAU GGAAAGG-5 (SEQ ID NO: 110)

TABLE 12 1099-1117 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 12-1 Unmodified siRNA + 84% 0% 5-ACCUUUCCACUUCUAAGCCTT (SEQ ID NO: 111) TTUGGAAAGGUGAAGAUUCGG-5 (SEQ ID NO: 112) 12-2 Random modification (2′-O-methyl) ++ 75% 41%  5-ACCUUUCCACUUCUAAGCCTT (SEQ ID NO: 113) TTUGGAAAGGUGAAGAUUCGG-5 (SEQ ID NO: 112) 12-3A Specific modification (2′-O-methyl) ++ 80% 15%  5-ACCUUUCCACUUCUAAGCCTT (SEQ ID NO: 111) TTUGGAAAGGUGAAGAU UCGG-5 (SEQ ID NO: 114) 12-3B Specific modification (2′-O-methyl) ++ 75% 6% 5-ACCUUUCCACUUC UAAGCCTT (SEQ ID NO: 115) TTUGGAAAGGUGAAGAU UCGG-5 (SEQ ID NO: 116)

TABLE 13 1111-1129 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 13-1 Unmodified siRNA + 90% 0% 5-CUAAGCCUGUUUCUUCCUCTT (SEQ ID NO: 117) TTGAUUCGGACAAAGAAGGAG-5 (SEQ ID NO: 118) 13-2 Random modification (2′-deoxy-2′-fluoro) ++ 75% 57%  5-CUAAGCCUGUUUCUUCCUCTT (SEQ ID NO: 119) TTGAUUCGGACAAAGAAGGAG-5 (SEQ ID NO: 120) 13-3A Specific modification (2′-deoxy-2′-fluoro) ++ 85% 12%  5-CUA AGCCUGUUUCUUCCUCTT (SEQ ID NO: 121) TTGAU UCGGACAAAGAAGGAG-5 (SEQ ID NO: 122) 13-3B Specific modification (2′-deoxy-2′-fluoro) ++ 82% 4% 5-C UAAGCCUGUUUCUUCCUCTT (SEQ ID NO: 123) TTGAUUCGGACAAAGAAGGAG-5 (SEQ ID NO: 118)

TABLE 14 2456-2474 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 14-1 Unmodified siRNA + 55% 0% 5-GAAGAUAGGAAGGGGCUUCTT (SEQ ID NO: 124) TTCUUCUAUCCUUCCCCGAAG-5 (SEQ ID NO: 125) 14-2 Random modification (2′-deoxy-2′-fluoro) ++  5% 23%  5-GAAGAUAGGAAGGGGCUUCTT (SEQ ID NO: 124) TTCUUCUAUCCUUCCCCGAAG-5 (SEQ ID NO: 126) 14-3A Specific modification (2′-deoxy-2′-fluoro) ++ 45% 9% 5-GAAGAU AGGAAGGGGCUUCTT (SEQ ID NO: 127) TTCUUCUAUCCUUCCCCGAAG-5 (SEQ ID NO: 125) 14-3B Specific modification (2′-deoxy-2′-fluoro) ++ 56% 4% 5-GAAGA UAGGAAGGGGCUUCTT (SEQ ID NO: 128) TTCUUCUAU CCUUCCCCGAAG-5 (SEQ ID NO: 129)

TABLE 15 294-312 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 15-1 Unmodified siRNA + 73% 0% 5-AAUAAGCAGCUCGCGCUCCTT (SEQ ID NO: 130) TTUUAUUCGUCGAGCGCGAGG-5 (SEQ ID NO: 131) 15-2 Random modification (2′-O-methyl) ++ 64% 23%  5-AAUAAGCAGCUCGCGCUCCTT (SEQ ID NO: 132) TTUUAUUCGUCGAGCGCGAGG-5 (SEQ ID NO: 131) 15-3A Specific modification (2′-O-methyl) ++ 68% 12%  5-AA UAAGCAGCUCGCGCUCCTT (SEQ ID NO: 133) TTUUAU UCGUCGAGCGCGAGG-5 (SEQ ID NO: 134) 15-3B Specific modification (2′-O-methyl) ++ 69% 4% 5-AA UAAGCAGCUCGCGCUCCTT (SEQ ID NO: 135) TTUUAU UCGUCGAGCGCGAGG-5 (SEQ ID NO: 136)

TABLE 16 673-691 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 16-1 Unmodified siRNA + 93% 0% 5-UAGCCAGAGCCAAAGAAGCTT (SEQ ID NO: 137) TTAUCGGUCUCGGUUUCUUCG-5 (SEQ ID NO: 138) 16-2 Random modification (2′-O-methyl) ++ 75% 57%  5-UAGCCAGAGCCAAAGAAGCTT (SEQ ID NO: 139) TTAUCGGUCUCGGUUUCUUCG-5 (SEQ ID NO: 140) 16-3A Specific modification (2′-O-methyl) ++ 85% 12%  5- UAGCCAGAGCCAAAGAAGCTT (SEQ ID NO: 141) TTAU CGGUCUCGGUUUCUUCG-5 (SEQ ID NO: 142) 16-3B Specific modification (2′-O-methyl) ++ 82% 4% 5- UAGCCAGAGCCAAAGAAGCTT (SEQ ID NO: 143) TTAU CGGUCUCGGUUUCUUCG-5 (SEQ ID NO: 144)

TABLE 17 1012-1030 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 17-1 Unmodified siRNA + 49% 0% 5-AACAGUCCUUAGCUACGCUTT (SEQ ID NO: 145) TTUUGUCAGGAAUCGAUGCGA-5 (SEQ ID NO: 146) 17-2 Random modification (2′-O-methyl) + 35% 57%  5-AACAGUCCUUAGCUACGCUTT (SEQ ID NO: 147) TTUUGUCAGGAAUCGAUGCGA-5 (SEQ ID NO: 146) 17-3A Specific modification (2′-O-methyl) ++ 85% 12%  5-AACAGUCCU UAGC UACGCUTT (SEQ ID NO: 148) TTUUGUCAGGAAU CGAU GCGA-5 (SEQ ID NO: 149) 17-3B Specific modification (2′-O-methyl) ++ 82% 4% 5-AACAGUCCU UAGC UACGCUTT (SEQ ID NO: 150) TTUUGUCAGGAAUCGAU GCGA-5 (SEQ ID NO: 151)

TABLE 18 1383-1401 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 18-1 Unmodified siRNA + 72% 0% 5-CUAGAGGAUCUUGAAGACCTT (SEQ ID NO: 152) TTGAUCUCCUAGAACUUCUGG-5 (SEQ ID NO: 153) 18-2 Random modification (2′-deoxy-2′-fluoro) ++ 12% 42%  5-CUAGAGGAUCUUGAAGACCTT (SEQ ID NO: 154) TTGAUCUCCUAGAACUUCUGG-5 (SEQ ID NO: 155) 18-3A Specific modification (2′-deoxy-2′-fluoro) ++ 67% 12%  5-C UAGAGGAUCUUGAAGACCTT (SEQ ID NO: 156) TTGAU CUCCUAGAACUUCUGG-5 (SEQ ID NO: 157) 18-3B Specific modification (2′-deoxy-2′-fluoro) ++ 82% 4% 5-CUA GAGGAUCUUGAAGACCTT (SEQ ID NO: 158) TTGAU CUCCUAGAACUUCUGG-5 (SEQ ID NO: 159)

TABLE 19 2151-2169 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 19-1 Unmodified siRNA + 52% 0% 5-AUCGACCUGAAGGAGUACGTT (SEQ ID NO: 160) TTUAGCUGGACUUCCUCAUGC-5 (SEQ ID NO: 161) 19-2 Random modification (2′-deoxy-2′-fluoro) ++ 21% 49%  5-AUCGACCUGAAGGAGUACGTT (SEQ ID NO: 162) TTUAGCUGGACUUCCUCAUGC-5 (SEQ ID NO: 163) 19-3A Specific modification (2′-deoxy-2′-fluoro) ++ 46% 9% 5-AUCGACCUGAAGGAG UACGTT (SEQ ID NO: 164) TTUAGCUGGACUUCCUCAU GC-5 (SEQ ID NO: 165) 19-3B Specific modification (2′-deoxy-2′-fluoro) ++ 82% 4% 5-AUCGACCUGAAGGAG UACGTT (SEQ ID NO: 166) TTUAGCUGGACUUCCUC AUGC-5 (SEQ ID NO: 167)

TABLE 20 2459-2477 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 20-1 Unmodified siRNA + 53% 0% 5-GAUAGGAAGGGGCUUCAGCTT (SEQ ID NO: 168) TTCUAUCCUUCCCCGAAGUCG-5 (SEQ ID NO: 169) 20-2 Random modification (2′-O-methyl) ++ 12% 52%  5-GAUAGGAAGGGGCUUCAGCTT (SEQ ID NO: 168) TTCUAUCCUUCCCCGAAGUCG-5 (SEQ ID NO: 170) 20-3A Specific modification (2′-O-methyl) ++ 42% 16%  5-GA UAGGAAGGGGCUUCAGCTT (SEQ ID NO: 171) TTCUAU CCUUCCCCGAAGUCG-5 (SEQ ID NO: 172) 20-3B Specific modification (2′-O-methyl) ++ 41% 6% 5-GA UAGGAAGGGGCUUCAGCTT (SEQ ID NO: 173) TTCU AU CCUUCCCCGAAGUCG-5 (SEQ ID NO: 174)

TABLE 21 2935-2953 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 21-1 Unmodified siRNA + 72% 0% 5-AGUCCCUGGAGCCUUAAACTT (SEQ ID NO: 175) TTUCAGGGACCUCGGAAUUUG-5 (SEQ ID NO: 176) 21-2 Random modification (2′-O-methyl) + 68% 41%  5-AGUCCCUGGAGCCUUAAACTT (SEQ ID NO: 177) TTUCAGGGACCUCGGAAUUUG-5 (SEQ ID NO: 176) 21-3A Specific modification (2′-O-methyl) ++ 65% 12%  5-AGUCCCUGGAGCCU UAAACTT (SEQ ID NO: 178) TTUCAGGGACCUCGGAAU UUG-5 (SEQ ID NO: 179) 21-3B Specific modification (2′-O-methyl) ++ 62% 5% 5-AGUCCCUGGAGCCU UA AACTT (SEQ ID NO: 180) TTUCAGGGACCUCGGA AUUUG-5 (SEQ ID NO: 181)

TABLE 22 3327-3345 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 22-1 Unmodified siRNA + 39% 0% 5-AGCCACAUUUCUAGGAGAUTT (SEQ ID NO: 182) TTUCGGUGUAAAGAUCCUCUA-5 (SEQ ID NO: 183) 22-2 Random modification (2′-O-methyl) ++ 19% 52%  5-AGCCACAUUUCUAGGAGAUTT (SEQ ID NO: 184) TTUCGGUGUAAAGAUCCUCUA-5 (SEQ ID NO: 183) 22-3A Specific modification (2′-O-methyl) ++ 26% 16%  5-AGCCACAUUUC UAGGAGAUTT (SEQ ID NO: 185) TTUCGGUGUAAAGAU CCUCUA-5 (SEQ ID NO: 186) 22-3B Specific modification (2′-O-methyl) ++ 29% 4% 5-AGCCACAUUUCUA GGAGAUTT (SEQ ID NO: 187) TTUCGGUGUAAAGAUCCUCUA-5 (SEQ ID NO: 188)

TABLE 23 3449-3467 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 23-1 Unmodified siRNA + 73% 0% 5-GAUUCCAAACCCCACUAUCTT (SEQ ID NO: 189) TTCUAAGGUUUGGGGUGAUAG-5 (SEQ ID NO: 190) 23-2 Random modification (2′-O-methyl) ++ 54% 57%  5-GAUUCCAAACCCCACUAUCTT (SEQ ID NO: 191) TTCUAAGGUUUGGGGUGAUAG-5 (SEQ ID NO: 190) 23-3A Specific modification (2′-O-methyl) ++ 67% 13%  5-GAUUCCAAACCCCAC UAUCTT (SEQ ID NO: 192) TTCUAAGGUUUGGGGUGAUAG-5 (SEQ ID NO: 193) 23-3B Specific modification (2′-O-methyl) ++ 69% 5% 5-GAUUCCAAACCCCAC UAUCTT (SEQ ID NO: 194) TTCUAAGGUUUGGGGUG AUAG-5 (SEQ ID NO: 195)

TABLE 24 3751-3769 BP human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 24-1 Unmodified siRNA + 53% 0% 5-GAUACUUCUGGUUCCCUCCTT (SEQ ID NO: 196) TTCUAUGAAGACCAAGGGAGG-5 (SEQ ID NO: 197) 24-2 Random modification (2′-O-methyl) ++ 45% 60%  5-GAUACUUCUGGUUCCCUCCTT (SEQ ID NO: 198) TTCUAUGAAGACCAAGGGAGG-5 (SEQ ID NO: 197) 24-3A Specific modification (2′-O-methyl) ++ 45% 10%  5-GA UACUUCUGGUUCCCUCCTT (SEQ ID NO: 199) TTCUAU GAAGACCAAGGGAGG-5 (SEQ ID NO: 200) 24-3B Specific modification (2′-O-methyl) ++ 46% 5% 5-GA UACUUCUGGUUCCCUCCTT (SEQ ID NO: 201) TTCUAU GAAGACCAAGGGAGG-5 (SEQ ID NO: 202)

TABLE 25 5508-5526 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 25-1 Unmodified siRNA + 83% 0% 5-AGAGAAGGGCGUCUCUACATT (SEQ ID NO: 203) TTUCUCUUCCCGCAGAGAUGU-5 (SEQ ID NO: 204) 25-2 Random modification (2′-deoxy-2′-fluoro) ++ 75% 49%  5-AGAGAAGGGCGUCUCUACATT (SEQ ID NO: 205) TTUCUCUUCCCGCAGAGAUGU-5 (SEQ ID NO: 204) 25-3A Specific modification (2′-deoxy-2′-fluoro) ++ 71% 16%  5-AGAGAAGGGCGUCUC UA CATT (SEQ ID NO: 206) TTUCUCUUCCCGCAGAGAU GU-5 (SEQ ID NO: 207) 25-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 4% 5-AGAGAAGGGCGUCUCUA CATT (SEQ ID NO: 208) TTUCUCUUCCCGCAGAGAU GU-5 (SEQ ID NO: 209)

TABLE 26 5939-5957 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 26-1 Unmodified siRNA + 90% 0% 5-AGUUUCUAGGGCCGUGGCCTT (SEQ ID NO: 210) TTUCAAAGAUCCCGGCACCGG-5 (SEQ ID NO: 211) 26-2 Random modification (2′-deoxy-2′-fluoro) ++ 75% 61%  5-AGUUUCUAGGGCCGUGGCCTT (SEQ ID NO: 212) TTUCAAAGAUCCCGGCACCGG-5 (SEQ ID NO: 211) 26-3A Specific modification (2′-deoxy-2′-fluoro) ++ 85% 13%  5-AGUUUC UAGGGCCGUGGCCTT (SEQ ID NO: 213) TTUCAAAGAU CCCGGCACCGG-5 (SEQ ID NO: 214) 26-3B Specific modification (2′-deoxy-2′-fluoro) ++ 82% 7% 5-AGUUUC UA GGGCCGUGGCCTT (SEQ ID NO: 215) TTUCAAAGAU CCCGGCACCGG-5 (SEQ ID NO: 216)

TABLE 27 587-605 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 27-1 Unmodified siRNA + 62% 0% 5-GAAGAGUUAACCCGGGACUTT (SEQ ID NO: 218) TTCUUCUCAAUUGGGCCCUGA-5 (SEQ ID NO: 219) 27-2 Random modification (2′-O-methyl) ++ 17% 61%  5-GAAGAGUUAACCCGGGACUTT (SEQ ID NO: 220) TTCUUCUCAAUUGGGCCCUGA-5 (SEQ ID NO: 219) 27-3A Specific modification (2′-O-methyl) ++ 47% 13%  5-GAAGAGU UAACCCGGGACUTT (SEQ ID NO: 221) TTCUUCUCAAU UGGGCCCUGA-5 (SEQ ID NO: 222) 27-3B Specific modification (2′-O-methyl) ++ 51% 6% 5-GAAGAGU UAACCCGGGACUTT (SEQ ID NO: 223) TTCUUCUCAAU UGGGCCCUGA-5 (SEQ ID NO: 224)

TABLE 28 808-826 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 28-1 Unmodified siRNA + 95% 0% 5-CCGCCCGGCGGCGCCUUUATT (SEQ ID NO: 225) TTGGCGGGCCGCCGCGGAAAU-5 (SEQ ID NO: 226) 28-2 Random modification (2′-O-methyl) ++ 49% 52%  5-CCGCCCGGCGGCGCCUUUATT (SEQ ID NO: 227) TTGGCGGGCCGCCGCGGAAAU-5 (SEQ ID NO: 226) 28-3A Specific modification (2′-O-methyl) ++ 85% 11%  5-CCGCCCGGCGGCGCCUU UA TT (SEQ ID NO: 228) TTGGCGGGCCGCCGCGGAA AU -5 (SEQ ID NO: 229) 28-3B Specific modification (2′-O-methyl) ++ 82% 4% 5-CCGCCCGGCGGCGCCUUUA TT (SEQ ID NO: 230) TTGGCGGGCCGCCGCGGAA AU -5 (SEQ ID NO: 231)

TABLE 29 941-959 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 29-1 Unmodified siRNA + 73% 0% 5-ACCGACGAUUCUUCUACUCTT (SEQ ID NO: 232) TTUGGCUGCUAAGAAGAUGAG-5 (SEQ ID NO: 233) 29-2 Random modification (2′-O-methyl) ++ 42% 47%  5-ACCGACGAUUCUUCUACUCTT (SEQ ID NO: 234) TTUGGCUGCUAAGAAGAUGAG-5 (SEQ ID NO: 233) 29-3A Specific modification (2′-O-methyl) ++ 67% 9% 5-ACCGACGAUUCUUC UACUCTT (SEQ ID NO: 235) TTUGGCUGCUAAGAAGAU GAG-5 (SEQ ID NO: 236) 29-3B Specific modification (2′-O-methyl) ++ 68% 4% 5-ACCGACGAUUCUUCUACUCTT (SEQ ID NO: 235) TTUGGCUGCUAAGAAGAU GAG-5 (SEQ ID NO: 237)

TABLE 30 2262-2280 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 30-1 Unmodified siRNA + 54% 0% 5-GGUAGAAUAGGUUUUCCCCTT (SEQ ID NO: 238) TTCCAUCUUAUCCAAAAGGGG-5 (SEQ ID NO: 239) 30-2 Random modification (2′-O-methyl) ++ 11% 71%  5-GGUAGAAUAGGUUUUCCCCTT (SEQ ID NO: 240) TTCCAUCUUAUCCAAAAGGGG-5 (SEQ ID NO: 239) 30-3A Specific modification (2′-O-methyl) ++ 45% 10%  5-GG UA GAA UAGGUUUUCCCCTT (SEQ ID NO: 241) TTCCAU CUUAU CCAAAAGGGG-5 (SEQ ID NO: 242) 30-3B Specific modification (2′-O-methyl) ++ 82% 3% 5-GG UAGAAUAGGUUUUCCCCTT (SEQ ID NO: 243) TTCCAUCUUAU CCAAAAGGGG-5 (SEQ ID NO: 244)

TABLE 31 15-33 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 31-1 Unmodified siRNA + 58% 0% 5-UCCCUUCCACCGCCAUAUUTT (SEQ ID NO: 245) TTAGGGAAGGUGGCGGUAUAA-5 (SEQ ID NO: 246) 31-2 Random modification (2′-O-methyl) ++ 11% 59%  5-UCCCUUCCACCGCCAUAUUTT (SEQ ID NO: 247) TTAGGGAAGGUGGCGGUAUAA-5 (SEQ ID NO: 246) 31-3A Specific modification (2′-O-methyl) ++ 47% 13%  5-UCCCUUCCACCGCCA UAUUTT (SEQ ID NO: 248) TTAGGGAAGGUGGCGGU AU AA-5 (SEQ ID NO: 249) 31-3B Specific modification (2′-O-methyl) ++ 49% 2% 5-UCCCUUCCACCGCCA UAUUTT (SEQ ID NO: 250) TTAGGGAAGGUGGCGGUAU AA-5 (SEQ ID NO: 251)

TABLE 32 485-503 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 32-1 Unmodified siRNA + 70% 0% 5-CGAGUGUCUAACGGGAGCCTT (SEQ ID NO: 252) TTGCUCACAGAUUGCCCUCGG-5 (SEQ ID NO: 253) 32-2 Random modification (2′-O-methyl) ++ 25% 56%  5-CGAGUGUCUAACGGGAGCCTT (SEQ ID NO: 254) TTGCUCACAGAUUGCCCUCGG-5 (SEQ ID NO: 253) 32-3A Specific modification (2′-O-methyl) ++ 65% 9% 5-CGAGUGUC UAACGGGAGCCTT (SEQ ID NO: 255) TTGCUCACAGAU UGCCCUCGG-5 (SEQ ID NO: 256) 32-3B Specific modification (2′-O-methyl) ++ 68% 2% 5-CGAGUGUCUAACGGGAGCCTT (SEQ ID NO: 252) TTGCUCACAGAU UGCCCUCGG-5 (SEQ ID NO: 257)

TABLE 33 581-599 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 33-1 Unmodified siRNA + 91% 0% 5-GACCACGAAGAGUUAACCCTT (SEQ ID NO: 258) TTCUGGUGCUUCUCAAUUGGG-5 (SEQ ID NO: 259) 33-2 Random modification (2′-deoxy-2′-fluoro) ++ 51% 59%  5-GACCACGAAGAGUUAACCCTT (SEQ ID NO: 260) TTCUGGUGCUUCUCAAUUGGG-5 (SEQ ID NO: 259) 33-3A Specific modification (2′-deoxy-2′-fluoro) ++ 85% 13%  5-GACCACGAAGAGU UAACCCTT (SEQ ID NO: 261) TTCUGGUGCUUCUCAAU UGGG-5 (SEQ ID NO: 262) 33-3B Specific modification (2′-deoxy-2′-fluoro) ++ 82% 7% 5-GACCACGAAGAGU UAACCCTT (SEQ ID NO: 263) TTCUGGUGCUUCUCAAU UGGG-5 (SEQ ID NO: 264)

TABLE 34 591-609 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 34-1 Unmodified siRNA + 97% 0% 5-AGUUAACCCGGGACUUGGATT (SEQ ID NO: 265) TTUCAAUUGGGCCCUGAACCU-5 (SEQ ID NO: 266) 34-2 Random modification (2′-deoxy-2′-fluoro) ++ 65% 57%  5-AGUUAACCCGGGACUUGGATT (SEQ ID NO: 267) TTUCAAUUGGGCCCUGAACCU-5 (SEQ ID NO: 266) 34-3A Specific modification (2′-deoxy-2′-fluoro) ++ 85% 9% 5-AGU UAACCCGGGACUUGGATT (SEQ ID NO: 268) TTUCAAU UGGGCCCUGAACCU-5 (SEQ ID NO: 269) 34-3B Specific modification (2′-deoxy-2′-fluoro) ++ 86% 4% 5-AGU UAACCCGGGACUUGGATT (SEQ ID NO: 270) TTUCAAU UGGGCCCUGAACCU-5 (SEQ ID NO: 271)

TABLE 35 669-687 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 35-1 Unmodified siRNA + 35% 0% 5-AUCACAAACCCCUAGAGGGTT (SEQ ID NO: 272) TTUAGUGUUUGGGGAUCUCCC-5 (SEQ ID NO: 273) 35-2 Random modification (2′-O-methyl) ++  9% 51%  5-AUCACAAACCCCUAGAGGGTT (SEQ ID NO: 274) TTUAGUGUUUGGGGAUCUCCC-5 (SEQ ID NO: 273) 35-3A Specific modification (2′-O-methyl) ++ 27% 10%  5-AUCACAAACCCC UAGAGGGTT (SEQ ID NO: 275) TTUAGUGUUUGGGGAU CUCCC-5 (SEQ ID NO: 276) 35-3B Specific modification (2′-O-methyl) ++ 29% 4% 5-AUCACAAACCCC UAGAGGGTT (SEQ ID NO: 277) TTUAGUGUUUGGGGAU CUCCC-5 (SEQ ID NO: 278)

TABLE 36 674-692 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 36-1 Unmodified siRNA + 81% 0% 5-AAACCCCUAGAGGGCAAGUTT (SEQ ID NO: 279) TTUUUGGGGAUCUCCCGUUCA-5 (SEQ ID NO: 280) 36-2 Random modification (2′-O-methyl) ++ 62% 54%  5-AAACCCCUAGAGGGCAAGUTT (SEQ ID NO: 281) TTUUUGGGGAUCUCCCGUUCA-5 (SEQ ID NO: 280) 36-3A Specific modification (2′-O-methyl) ++ 78% 11%  5-AAACCCC UAGAGGGCAAGUTT (SEQ ID NO: 282) TTUUUGGGGAU CUCCCGUUCA-5 (SEQ ID NO: 283) 36-3B Specific modification (2′-O-methyl) ++ 75% 5% 5-AAACCCC UAGAGGGCAAGUTT (SEQ ID NO: 284) TTUUUGGGGAU CUCCCGUUCA-5 (SEQ ID NO: 285)

TABLE 37 835-853 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 37-1 Unmodified siRNA + 95% 0% 5-UCCGGCUAACUCUGAGGACTT (SEQ ID NO: 286) TTAGGCCGAUUGAGACUCCUG-5 (SEQ ID NO: 286) 37-2 Random modification (2′-deoxy-2′-fluoro) ++ 41% 61%  5-UCCGGCUAACUCUGAGGACTT (SEQ ID NO: 286) TTAGGCCGAUUGAGACUCCUG-5 (SEQ ID NO: 286) 37-3A Specific modification (2′-deoxy-2′-fluoro) ++ 85% 9% 5-UCCGGC UAACUCUGAGGACTT (SEQ ID NO: 286) TTAGGCCGAU UGAGACUCCUG-5 (SEQ ID NO: 290) 37-3B Specific modification (2′-deoxy-2′-fluoro) ++ 82% 3% 5-UCCGGC UAACUCUGAGGACTT (SEQ ID NO: 291) TTAGGCCGAU UGAGACUCCUG-5 (SEQ ID NO: 292)

TABLE 38 943-961 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 38-1 Unmodified siRNA + 72% 0% 5-CGACGAUUCUUCUACUCAATT (SEQ ID NO: 293) TTGCUGCUAAGAAGAUGAGUU-5 (SEQ ID NO: 294) 38-2 Random modification (2′-deoxy-2′-fluoro) ++ 56% 34%  5-CGACGAUUCUUCUACUCAATT (SEQ ID NO: 295) TTGCUGCUAAGAAGAUGAGUU-5 (SEQ ID NO: 294) 38-3A Specific modification (2′-deoxy-2′-fluoro) ++ 62% 9% 5-CGACGAUUCUUC UACUCAATT (SEQ ID NO: 296) TTGCUGCUAAGAAGAU GAGUU-5 (SEQ ID NO: 297) 38-3B Specific modification (2′-deoxy-2′-fluoro) ++ 67% 4% 5-CGACGAUUCUUC UACUCAATT (SEQ ID NO: 298) TTGCUGCUAAGAAGAU GAGUU-5 (SEQ ID NO: 299)

TABLE 39 1353-1371 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 39-1 Unmodified siRNA + 73% 0% 5-UAAACUUUGGGGAAGGGAGTT (SEQ ID NO: 300) TTAUUUGAAACCCCUUCCCUC-5 (SEQ ID NO: 301) 39-2 Random modification (2′-O-methyl) ++ 34% 48%  5-UAAACUUUGGGGAAGGGAGTT (SEQ ID NO: 302) TTAUUUGAAACCCCUUCCCUC-5 (SEQ ID NO: 301) 39-3A Specific modification (2′-O-methyl) ++ 67% 11%  5- UAAACUUUGGGGAAGGGAGTT (SEQ ID NO: 303) TTAU UUGAAACCCCUUCCCUC-5 (SEQ ID NO: 304) 39-3B Specific modification (2′-O-methyl) ++ 72% 3% 5- UAAACUUUGGGGAAGGGAGTT (SEQ ID NO: 305) TTAU UUGAAACCCCUUCCCUC-5 (SEQ ID NO: 306)

TABLE 40 1401-1419 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 40-1 Unmodified siRNA + 95% 0% 5-AGCGGGGUAUGAAGAGCUUTT (SEQ ID NO: 307) TTUCGCCCCAUACUUCUCGAA-5 (SEQ ID NO: 308) 40-2 Random modification (2′-O-methyl) ++ 75% 38%  5-AGCGGGGUAUGAAGAGCUUTT (SEQ ID NO: 309) TTUCGCCCCAUACUUCUCGAA-5 (SEQ ID NO: 308) 40-3A Specific modification (2′-O-methyl) ++ 85% 13%  5-AGCGGGG UA UGAAGAGCUUTT (SEQ ID NO: 310) TTUCGCCCCAU ACUUCUCGAA-5 (SEQ ID NO: 311) 40-3B Specific modification (2′-O-methyl) ++ 82% 6% 5-AGCGGGG UAUGAAGAGCUUTT (SEQ ID NO: 312) TTUCGCCCCAU ACUUCUCGAA-5 (SEQ ID NO: 313)

TABLE 41 1711-1729 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth inhibition gene SIRNA Stability inhibition ratio ratio 41-1 Unmodified siRNA + 72% 0% 5-CUCCCCAGUCUCUCUUAAATT (SEQ ID NO: 314) TTGAGGGGUCAGAGAGAAUUU-5 (SEQ ID NO: 315) 41-2 Random modification (2′-O-methyl) ++ 51% 46%  5-CUCCCCAGUCUCUCUUAAATT (SEQ ID NO: 316) TTGAGGGGUCAGAGAGAAUUU-5 (SEQ ID NO: 315) 41-3A Specific modification (2′-O-methyl) ++ 68% 15%  5-CUCCCCAGUCUCUCU UAAATT (SEQ ID NO: 317) TTGAGGGGUCAGAGAGAAU UU-5 (SEQ ID NO: 318) 41-3B Specific modification (2′-O-methyl) ++ 69% 7% 5-CUCCCCAGUCUCUCUUA AATT (SEQ ID NO: 319) TTGAGGGGUCAGAGAGA AUUU-5 (SEQ ID NO: 320)

TABLE 42 108-126 BP chimpanzee SOD2(NM_001009022) (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 42-1 Unmodified siRNA + 59% 0% 5-GAAUAACCUGAACGUCACCTT (SEQ ID NO: 322) TTCUUAUUGGACUUGCAGUGG-5 (SEQ ID NO: 323) 42-2 Random modification (2′-O-methyl) ++ 17% 49%  5-GAAUAACCUGAACGUCACCTT (SEQ ID NO: 324) TTCUUAUUGGACUUGCAGUGG-5 (SEQ ID NO: 323) 42-3A Specific modification (2′-O-methyl) ++ 51% 12%  5-GAA UAACCUGAACGUCACCTT (SEQ ID NO: 325) TTCUUAU UGGACUUGCAGUGG-5 (SEQ ID NO: 326) 42-3B Specific modification (2′-O-methyl) ++ 55% 4% 5-GAA UAACCUGAACGUCACCTT (SEQ ID NO: 327) TTCUUAU UGGACUUGCAGUGG-5 (SEQ ID NO: 328)

TABLE 43 119-137 BP Chimpanzee SOD2(NM_001009022) (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 43-1 Unmodified siRNA + 65% 0% 5-ACGUCACCGAGGAGAAGUATT (SEQ ID NO: 329) TTUGCAGUGGCUCCUCUUCAU-5 (SEQ ID NO: 330) 43-2 Random modification (2′-O-methyl) ++ 36% 46%  5-ACGUCACCGAGGAGAAGUATT (SEQ ID NO: 331) TTUGCAGUGGCUCCUCUUCAU-5 (SEQ ID NO: 330) 43-3A Specific modification (2′-O-methyl) ++ 48% 8% 5-ACGUCACCGAGGAGAAG UATT (SEQ ID NO: 332) TTUGCAGUGGCUCCUCUUCAU-5 (SEQ ID NO: 333) 43-3B Specific modification (2′-O-methyl) ++ 69% 2% 5-ACGUCACCGAGGAGAAG UATT (SEQ ID NO: 334) TTUGCAGUGGCUCCUCUUCAU-5 (SEQ ID NO: 330)

TABLE 44 131-149 BP Chimpanzee SOD2(NM_001009022) (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 44-1 Unmodified siRNA + 75% 0% 5-AGAAGUACCAGGAGGCGUUTT (SEQ ID NO: 335) TTUCUUCAUGGUCCUCCGCAA-5 (SEQ ID NO: 336) 44-2 Random modification (2′-O-methyl) ++ 24% 39%  5-AGAAGUACCAGGAGGCGUUTT (SEQ ID NO: 337) TTUCUUCAUGGUCCUCCGCAA-5 (SEQ ID NO: 336) 44-3A Specific modification (2′-O-methyl) ++ 68% 9% 5-AGAAG UACCAGGAGGCGUUTT (SEQ ID NO: 338) TTUCUUCAU GGUCCUCCGCAA-5 (SEQ ID NO: 339) 44-3B Specific modification (2′-O-methyl) ++ 69% 3% 5-AGAAG UACCAGGAGGCGUUTT (SEQ ID NO: 340) TTUCUUCAU GGUCCUCCGCAA-5 (SEQ ID NO: 341)

TABLE 45 168-186 BP Chimpanzee SOD2(NM_001009022) (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 45-1 Unmodified siRNA + 72% 0% 5-AGCCCAGAUAGCUCUUCAGTT (SEQ ID NO: 342) TTUCGGGUCUAUCGAGAAGUC-5 (SEQ ID NO: 343) 45-2 Random modification (2′-deoxy-2′-fluoro) ++ 35% 46%  5-AGCCCAGAUAGCUCUUCAGTT (SEQ ID NO: 344) TTUCGGGUCUAUCGAGAAGUC-5 (SEQ ID NO: 343) 45-3A Specific modification (2′-deoxy-2′-fluoro) ++ 61% 12%  5-AGCCCAGA UAGCUCUUCAGTT (SEQ ID NO: 345) TTUCGGGUCUAU CGAGAAGUC-5 (SEQ ID NO: 346) 45-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 5% 5-AGCCCAGA UAGCUCUUCAGTT (SEQ ID NO: 347) TTUCGGGUCUAU CGAGAAGUC-5 (SEQ ID NO: 348)

TABLE 46 240-258 BP Chimpanzee SOD2(NM_001009022) (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 46-1 Unmodified siRNA + 94% 0% 5-AAACCUCAGCCCUAACGGUTT (SEQ ID NO: 349) TTUUUGGAGUCGGGAUUGCCA-5 (SEQ ID NO: 350) 46-2 Random modification (2′-O-methyl) ++ 51% 62%  5-AAACCUCAGCCCUAACGGUTT (SEQ ID NO: 351) TTUUUGGAGUCGGGAUUGCCA-5 (SEQ ID NO: 350) 46-3A Specific modification (2′-O-methyl) ++ 79% 10%  5-AAACCUCAGCCC UAACGGUTT (SEQ ID NO: 352) TTUUUGGAGUCGGGAU UGCCA-5 (SEQ ID NO: 353) 46-3B Specific modification (2′-O-methyl) ++ 69% 6% 5-AAACCUCAGCCC UA ACGGUTT (SEQ ID NO: 354) TTUUUGGAGUCGGGAU UGCCA-5 (SEQ ID NO: 355)

TABLE 47 323-341 BP Chimpanzee SOD2(NM_001009022) (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 47-1 Unmodified siRNA + 73% 0% 5-UUAAGGAGAAGCUGACGGCTT (SEQ ID NO: 356) TTAAUUCCUCUUCGACUGCCG-5 (SEQ ID NO: 357) 47-2 Random modification (2′-O-methyl) ++ 24% 35%  5-UUAAGGAGAAGCUGACGGCTT (SEQ ID NO: 358) TTAAUUCCUCUUCGACUGCCG-5 (SEQ ID NO: 357) 47-3A Specific modification (2′-O-methyl) ++ 67% 12%  5-U UAAGGAGAAGCUGACGGCTT (SEQ ID NO: 359) TTAAU UCCUCUUCGACUGCCG-5 (SEQ ID NO: 360) 47-3B Specific modification (2′-O-methyl) ++ 69% 3% 5-U UAAGGAGAAGCUGACGGCTT (SEQ ID NO: 361) TTAAU UCCUCUUCGACUGCCG-5 (SEQ ID NO: 362)

TABLE 48 Chimpanzee SOD2(NM_001009022) 391-409 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 48-1 Unmodified siRNA + 44% 0% 5-AAGGAACGGGGACACUUACTT (SEQ ID NO: 363) TTUUCCUUGCCCCUGUGAAUG-5 (SEQ ID NO: 364) 48-2 Random modification (2′-O-methyl) ++ 12% 46%  5-AAGGAACGGGGACACUUACTT (SEQ ID NO: 365) TTUUCCUUGCCCCUGUGAAUG-5 (SEQ ID NO: 364) 48-3A Specific modification (2′-O-methyl) ++ 35% 15%  5-AAGGAACGGGGACACU UACTT (SEQ ID NO: 366) TTUUCCUUGCCCCUGUGAAU G-5 (SEQ ID NO: 367) 48-3B Specific modification (2′-O-methyl) ++ 38% 6% 5-AAGGAACGGGGACACUUACTT (SEQ ID NO: 363) TTUUCCUUGCCCCUGUGAAU G-5 (SEQ ID NO: 368)

TABLE 49 Chimpanzee SOD2(NM_001009022) 486-504 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 49-1 Unmodified siRNA + 77% 0% 5-GGAGCACGCUUACUACCUUTT (SEQ ID NO: 369) TTCCUCGUGCGAAUGAUGGAA-5 (SEQ ID NO: 370) 49-2 Random modification (2′-O-methyl) ++ 51% 38%  5-GGAGCACGCUUACUACCUUTT (SEQ ID NO: 371) TTCCUCGUGCGAAUGAUGGAA-5 (SEQ ID NO: 370) 49-3A Specific modification (2′-O-methyl) ++ 68% 13%  5-GGAGCACGCU UAC UACCUUTT (SEQ ID NO: 372) TTCCUCGUGCGAAU GAU GGAA-5 (SEQ ID NO: 373) 49-3B Specific modification (2′-O-methyl) ++ 69% 7% 5-GGAGCACGCU UAC UACCUUTT (SEQ ID NO: 374) TTCCUCGUGCGAAU GAU GGAA-5 (SEQ ID NO: 375)

TABLE 50 Rhesus monkey RECEPTOR(XM_001111972) 168-186 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 50-1 Unmodified siRNA + 77% 0% 5-GGCGGGCUCUUUCCUAUUCTT (SEQ ID NO: 376) TTCCGCCCGAGAAAGGAUAAG-5 (SEQ ID NO: 377) 50-2 Random modification (2′-O-methyl) ++ 51% 43%  5-GGCGGGCUCUUUCCUAUUCTT (SEQ ID NO: 378) TTCCGCCCGAGAAAGGAUAAG-5 (SEQ ID NO: 377) 50-3A Specific modification (2′-O-methyl) ++ 68% 8% 5-GGCGGGCUCUUUCC UAUUCTT (SEQ ID NO: 379) TTCCGCCCGAGAAAGGAU AAG-5 (SEQ ID NO: 380) 50-3B Specific modification (2′-O-methyl) ++ 69% 5% 5-GGCGGGCUCUUUCC UAUUCTT (SEQ ID NO: 381) TTCCGCCCGAGAAAGGAU AAG-5 (SEQ ID NO: 382)

TABLE 51 Rhesus monkey RECEPTOR(XM_001111972) 2006-2024 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 51-1 Unmodified siRNA + 80% 0% 5-CCGAGAGCUCUCCUACCUUTT (SEQ ID NO: 384) TTGGCUCUCGAGAGGAUGGAA-5 (SEQ ID NO: 385) 51-2 Random modification (2′-O-methyl) ++ 34% 43%  5-CCGAGAGCUCUCCUACCUUTT (SEQ ID NO: 386) TTGGCUCUCGAGAGGAUGGAA-5 (SEQ ID NO: 385) 51-3A Specific modification (2′-O-methyl) ++ 72% 12%  5-CCGAGAGCUCUCC UACCUUTT (SEQ ID NO: 387) TTGGCUCUCGAGAGGAU GGAA-5 (SEQ ID NO: 388) 51-3B Specific modification (2′-O-methyl) ++ 75% 5% 5-CCGAGAGCUCUCC UACCUUTT (SEQ ID NO: 389) TTGGCUCUCGAGAGGAU GGAA-5 (SEQ ID NO: 390)

TABLE 52 Rhesus monkey RECEPTOR(XM_001111972) 2013-2031 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 52-1 Unmodified siRNA + 83% 0% 5-CUCUCCUACCUUCUCCUCUTT (SEQ ID NO: 391) TTGAGAGGAUGGAAGAGGAGA-5 (SEQ ID NO: 392) 52-2 Random modification (2′-deoxy-2′-fluoro) ++ 69% 37%  5-CUCUCCUACCUUCUCCUCUTT (SEQ ID NO: 393) TTGAGAGGAUGGAAGAGGAGA-5 (SEQ ID NO: 392) 52-3A Specific modification (2′-deoxy-2′-fluoro) ++ 73% 6% 5-CUCUCC UACCUUCUCCUCUTT (SEQ ID NO: 394) TTGAGAGGAU GGAAGAGGAGA-5 (SEQ ID NO: 395) 52-3B Specific modification (2′-deoxy-2′-fluoro) ++ 78% 1% 5-CUCUCCUA CCUUCUCCUCUTT (SEQ ID NO: 396) TTGAGAGGAUGGAAGAGGAGA-5 (SEQ ID NO: 395)

TABLE 53 Rhesus monkey RECEPTOR(XM_001111972) 2018-2036 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 53-1 Unmodified siRNA + 75% 0% 5-CUACCUUCUCCUCUUCUCCTT (SEQ ID NO: 397) TTGAUGGAAGAGGAGAAGAGG-5 (SEQ ID NO: 398) 53-2 Random modification (2′-O-methyl) ++ 27% 38%  5-CUACCUUCUCCUCUUCUCCTT (SEQ ID NO: 399) TTGAUGGAAGAGGAGAAGAGG-5 (SEQ ID NO: 398) 53-3A Specific modification (2′-O-methyl) ++ 68% 5% 5-C UA CCUUCUCCUCUUCUCCTT (SEQ ID NO: 400) TTG AU GGAAGAGGAGAAGAGG-5 (SEQ ID NO: 401) 53-3B Specific modification (2′-O-methyl) ++ 69% 2% 5-C UACCUUCUCCUCUUCUCCTT (SEQ ID NO: 402) TTGAU GGAAGAGGAGAAGAGG-5 (SEQ ID NO: 403)

TABLE 54 Rhesus monkey RECEPTOR(XM_001111972) 13-31 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 54-1 Unmodified siRNA + 43% 0% 5-AGCCUCCAAACUCCUAGCUTT (SEQ ID NO: 404) TTUCGGAGGUUUGAGGAUCGA-5 (SEQ ID NO: 405) 54-2 Random modification (2′-deoxy-2′-fluoro) ++ 16% 34%  5-AGCCUCCAAACUCCUAGCUTT (SEQ ID NO: 406) TTUCGGAGGUUUGAGGAUCGA-5 (SEQ ID NO: 405) 54-3A Specific modification (2′-deoxy-2′-fluoro) ++ 32% 9% 5-AGCCUCCAAACUCC UAGCUTT (SEQ ID NO: 407) TTUCGGAGGUUUGAGGAU CGA-5 (SEQ ID NO: 408) 54-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 3% 5-AGCCUCCAAACUCC UAGCUTT (SEQ ID NO: 409) TTUCGGAGGUUUGAGGAU CGA-5 (SEQ ID NO: 410)

TABLE 55 Rhesus monkey RECEPTOR(XM_001111972) 24-42 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 55-1 Unmodified siRNA + 75% 0% 5-UCCUAGCUGUCUUGUCCCUTT (SEQ ID NO: 411) TTAGGAUCGACAGAACAGGGA-5 (SEQ ID NO: 412) 55-2 Random modification (2′-O-methyl) ++ 27% 33%  5-UCCUAGCUGUCUUGUCCCUTT (SEQ ID NO: 413) TTAGGAUCGACAGAACAGGGA-5 (SEQ ID NO: 412) 55-3A Specific modification (2′-O-methyl) ++ 68% 8% 5-UCC UAGCUGUCUUGUCCCUTT (SEQ ID NO: 414) TTAGGAU CGACAGAACAGGGA-5 (SEQ ID NO: 415) 55-3B Specific modification (2′-O-methyl) ++ 71% 1% 5-UCC UAGCUGUCUUGUCCCUTT (SEQ ID NO: 416) TTAGGAU CGACAGAACAGGGA-5 (SEQ ID NO: 417)

TABLE 56 Rhesus monkey RECEPTOR(XM_001111972) 162-180 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 56-1 Unmodified siRNA + 53% 0% 5-AUACUUGGCGGGCUCUUUCTT (SEQ ID NO: 418) TTUAUGAACCGCCCGAGAAAG-5 (SEQ ID NO: 419) 56-2 Random modification (2′-O-methyl) ++ 19% 35%  5-AUACUUGGCGGGCUCUUUCTT (SEQ ID NO: 420) TTUAUGAACCGCCCGAGAAAG-5 (SEQ ID NO: 419) 56-3A Specific modification (2′-O-methyl) ++ 42% 6% 5-A UACUUGGCGGGCUCUUUCTT (SEQ ID NO: 421) TTUAU GAACCGCCCGAGAAAG-5 (SEQ ID NO: 422) 56-3B Specific modification (2′-O-methyl) ++ 48% 1% 5-A UACUUGGCGGGCUCUUUCTT (SEQ ID NO: 423) TTUAUGAACCGCCCGAGAAAG-5 (SEQ ID NO: 424)

TABLE 57 Rhesus monkey RECEPTOR(XM_001111972) 536-554 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 57-1 Unmodified siRNA + 77% 0% 5-GGGGCUCUUCUACAUUCCCTT (SEQ ID NO: 424) TTCCCCGAGAAGAUGUAAGGG-5 (SEQ ID NO: 425) 57-2 Random modification (2′-O-methyl) ++ 51% 34%  5-GGGGCUCUUCUACAUUCCCTT (SEQ ID NO: 426) TTCCCCGAGAAGAUGUAAGGG-5 (SEQ ID NO: 425) 57-3A Specific modification (2′-O-methyl) ++ 68% 5% 5-GGGGCUCUUC UACAUUCCCTT (SEQ ID NO: 427) TTCCCCGAGAAGAU GUAAGGG-5 (SEQ ID NO: 428) 57-3B Specific modification (2′-O-methyl) ++ 72% 2% 5-GGGGCUCUUCUA CAUUCCCTT (SEQ ID NO: 429) TTCCCCGAGAAGAU GUAAGGG-5 (SEQ ID NO: 430)

TABLE 58 Rhesus monkey RECEPTOR(XM_001111972) 669-687 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 58-1 Unmodified siRNA + 87% 0% 5-GAGUAUUUCCGCUGGAACUTT (SEQ ID NO: 431) TTCUCAUAAAGGCGACCUUGA-5 (SEQ ID NO: 432) 58-2 Random modification (2′-deoxy-2′-fluoro) ++ 21% 37%  5-GAGUAUUUCCGCUGGAACUTT (SEQ ID NO: 433) TTCUCAUAAAGGCGACCUUGA-5 (SEQ ID NO: 432) 58-3A Specific modification (2′-deoxy-2′-fluoro) ++ 73% 6% 5-GAG UAUUUCCGCUGGAACUTT (SEQ ID NO: 434) TTCUCAU AAAGGCGACCUUGA-5 (SEQ ID NO: 435) 58-3B Specific modification (2′-deoxy-2′-fluoro) ++ 75% 1% 5-GAG UAUUUCCGCUGGAACUTT (SEQ ID NO: 436) TTCUCAU AAAGGCGACCUUGA-5 (SEQ ID NO: 437)

TABLE 59 Rhesus monkey RECEPTOR(XM_001111972) 753-771 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 59-1 Unmodified siRNA + 85% 0% 5-GCUGAGGAAAGGGACAUCUTT (SEQ ID NO: 438) TTCGACUCCUUUCCCUGUAGA-5 (SEQ ID NO: 439) 59-2 Random modification (2′-O-methyl) ++ 61% 31%  5-GCUGAGGAAAGGGACAUCUTT (SEQ ID NO: 440) TTCGACUCCUUUCCCUGUAGA-5 (SEQ ID NO: 439) 59-3A Specific modification (2′-O-methyl) ++ 76% 7% 5-GCUGAGGAAAGGGAC AUCUTT (SEQ ID NO: 441) TTCGACUCCUUUCCCUG UAGA-5 (SEQ ID NO: 442) 59-3B Specific modification (2′-O-methyl) ++ 78% 3% 5-GCUGAGGAAAGGGACAUCUTT (SEQ ID NO: 441) TTCGACUCCUUUCCCUG UA GA-5 (SEQ ID NO: 443)

TABLE 60 Rhesus monkey RECEPTOR(XM_001111972) 800-818 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 60-1 Unmodified siRNA + 75% 0% 5-GUACUCUGAUGAGGAAGAGTT (SEQ ID NO: 444) TTCAUGAGACUACUCCUUCUC-5 (SEQ ID NO: 445) 60-2 Random modification (2′-O-methyl) ++ 18% 37%  5-GUACUCUGAUGAGGAAGAGTT (SEQ ID NO: 446) TTCAUGAGACUACUCCUUCUC-5 (SEQ ID NO: 445) 60-3A Specific modification (2′-O-methyl) ++ 68% 8% 5-G UACUCUGAUGAGGAAGAGTT (SEQ ID NO: 447) TTCAU GAGACUACUCCUUCUC-5 (SEQ ID NO: 448) 60-3B Specific modification (2′-O-methyl) ++ 69% 1% 5-G UACUCUGAUGAGGAAGAGTT (SEQ ID NO: 449) TTCAUGAGACUACUCCUUCUC-5 (SEQ ID NO: 448)

TABLE 61 Rhesus monkey RECEPTOR(XM_001111972) 854-872 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 61-1 Unmodified siRNA + 93% 0% 5-GGCCAAAGUAAUCGUGGUUTT (SEQ ID NO: 450) TTCCGGUUUCAUUAGCACCAA-5 (SEQ ID NO: 451) 61-2 Random modification (2′-O-methyl) ++ 37% 31%  5-GGCCAAAGUAAUCGUGGUUTT (SEQ ID NO: 452) TTCCGGUUUCAUUAGCACCAA-5 (SEQ ID NO: 451) 61-3A Specific modification (2′-O-methyl) ++ 86% 10%  5-GGCCAAAG UAAUCGUGGUUTT (SEQ ID NO: 453) TTCCGGUUUCAU UAGCACCAA-5 (SEQ ID NO: 454) 61-3B Specific modification (2′-O-methyl) ++ 85% 5% 5-GGCCAAAG UAAUCGUGGUUTT (SEQ ID NO: 455) TTCCGGUUUCAU UAGCACCAA-5 (SEQ ID NO: 456)

TABLE 62 Rhesus monkey RECEPTOR(XM_001111972) 1602-1620 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 62-1 Unmodified siRNA + 81% 0% 5-GUCUAUGCCAAGAAGGGAGTT (SEQ ID NO: 457) TTCAGAUACGGUUCUUCCCUC-5 (SEQ ID NO: 458) 62-2 Random modification (2′-O-methyl) ++ 24% 31%  5-GUCUAUGCCAAGAAGGGAGTT (SEQ ID NO: 459) TTCAGAUACGGUUCUUCCCUC-5 (SEQ ID NO: 458) 62-3A Specific modification (2′-O-methyl) ++ 72% 7% 5-GUC UA UGCCAAGAAGGGAGTT (SEQ ID NO: 460) TTCAGAU ACGGUUCUUCCCUC-5 (SEQ ID NO: 461) 62-3B Specific modification (2′-O-methyl) ++ 76% 2% 5-GUC UAUGCCAAGAAGGGAGTT (SEQ ID NO: 462) TTCAGAU ACGGUUCUUCCCUC-5 (SEQ ID NO: 463)

TABLE 63 Rhesus monkey RECEPTOR(XM_001111972) 2293-2311 BP (SEQ ID NO: 383) Locus Expression  Growth  gene SIRNA Stability inhibition ratio inhibition ratio 63-1 Unmodified siRNA + 84% 0% 5-UCUACACCGCGCCCCCCUCTT (SEQ ID NO: 464) TTAGAUGUGGCGCGGGGGGAG-5 (SEQ ID NO: 465) 63-2 Random modification (2′-O-methyl) ++ 39% 33%  5-UCUACACCGCGCCCCCCUCTT (SEQ ID NO: 466) TTAGAUGUGGCGCGGGGGGAG-5 (SEQ ID NO: 465) 63-3A Specific modification (2′-O-methyl) ++ 73% 6% 5-UC UA CACCGCGCCCCCCUCTT (SEQ ID NO: 467) TTAGAU GUGGCGCGGGGGGAG-5 (SEQ ID NO: 468) 63-3B Specific modification (2′-O-methyl) ++ 79% 3% 5-UC UACACCGCGCCCCCCUCTT (SEQ ID NO: 469) TTAGAU GUGGCGCGGGGGGAG-5 (SEQ ID NO: 470)

TABLE 64 Rhesus monkey RECEPTOR(XM_001111972) 2302-2320 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 64-1 Unmodified siRNA + 81% 0% 5-CGCCCCCCUCAAGCUACCGTT (SEQ ID NO: 471) TTGCGGGGGGAGUUCGAUGGC-5 (SEQ ID NO: 472) 64-2 Random modification (2′-O-methyl) ++ 44% 48%  5-CGCCCCCCUCAAGCUACCGTT (SEQ ID NO: 473) TTGCGGGGGGAGUUCGAUGGC-5 (SEQ ID NO: 472) 64-3A Specific modification (2′-O-methyl) ++ 72% 9% 5-CGCCCCCCUCAAGC UACCGTT (SEQ ID NO: 474) TTGCGGGGGGAGUUCGAU GGC-5 (SEQ ID NO: 475) 64-3B Specific modification (2′-O-methyl) ++ 76% 3% 5-CGCCCCCCUCAAGC UACCGTT (SEQ ID NO: 476) TTGCGGGGGGAGUUCGAU GGC-5 (SEQ ID NO: 477)

TABLE 65 Rhesus monkey RECEPTOR(XM_001111972) 2314-2332 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 65-1 Unmodified siRNA + 47% 0% 5-GCUACCGCAACCACGAGCUTT (SEQ ID NO: 478) TTCGAUGGCGUUGGUGCUCGA-5 (SEQ ID NO: 479) 65-2 Random modification (2′-deoxy-2′-fluoro) ++ 21% 37%  5-GCUACCGCAACCACGAGCUTT (SEQ ID NO: 480) TTCGAUGGCGUUGGUGCUCGA-5 (SEQ ID NO: 479) 65-3A Specific modification (2′-deoxy-2′-fluoro) ++ 42% 7% 5-GC UACCGCAACCACGAGCUTT (SEQ ID NO: 481) TTCGAU GGCGUUGGUGCUCGA-5 (SEQ ID NO: 482) 65-3B Specific modification (2′-deoxy-2′-fluoro) ++ 45% 3% 5-GC UACCGCAACCACGAGCUTT (SEQ ID NO: 483) TTCGAU GGCGUUGGUGCUCGA-5 (SEQ ID NO: 484)

TABLE 66 Rhesus monkey RECEPTOR(XM_001111972) 2522-2540 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 66-1 Unmodified siRNA + 84% 0% 5-CUCCUUCAUUCCAGCCUAUTT (SEQ ID NO: 485) TTGAGGAAGUAAGGUCGGAUA-5 (SEQ ID NO: 486) 66-2 Random modification (2′-O-methyl) ++ 51% 31%  5-CUCCUUCAUUCCAGCCUAUTT (SEQ ID NO: 487) TTGAGGAAGUAAGGUCGGAUA-5 (SEQ ID NO: 486) 66-3A Specific modification (2′-O-methyl) ++ 78% 8% 5-CUCCUUCAUUCCAGCC UAUTT (SEQ ID NO: 488) TTGAGGAAGUAAGGUCGGAU A-5 (SEQ ID NO: 489) 66-3B Specific modification (2′-O-methyl) ++ 81% 4% 5-CUCCUUCAUUCCAGCC UAUTT (SEQ ID NO: 490) TTGAGGAAGUAAGGUCGGAU A-5 (SEQ ID NO: 491)

TABLE 67 Rhesus monkey RECEPTOR(XM_001111972) 2998-3016 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 67-1 Unmodified siRNA + 78% 0% 5-AGAAAAGCAGCGAUACGCUTT (SEQ ID NO: 492) TTUCUUUUCGUCGCUAUGCGA-5 (SEQ ID NO: 493) 67-2 Random modification (2′-O-methyl) ++ 34% 37%  5-AGAAAAGCAGCGAUACGCUTT (SEQ ID NO: 494) TTUCUUUUCGUCGCUAUGCGA-5 (SEQ ID NO: 493) 67-3A Specific modification (2′-O-methyl) ++ 68% 8% 5-AGAAAAGCAGCGA UACGCUTT (SEQ ID NO: 495) TTUCUUUUCGUCGCUAUGCGA-5 (SEQ ID NO: 496) 67-3B Specific modification (2′-O-methyl) ++ 69% 1% 5-AGAAAAGCAGCGA UACGCUTT (SEQ ID NO: 497) TTUCUUUUCGUCGCUAUGCGA-5 (SEQ ID NO: 493)

TABLE 68 Dog B cell lymphoma(NM_001003016) 480-498 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 68-1 Unmodified siRNA + 93% 0% 5-GGAGCUAGACGGGUACGAGTT (SEQ ID NO: 499) TTCCUCGAUCUGCCCAUGCUC-5 (SEQ ID NO: 500) 68-2 Random modification (2′-O-methyl) ++ 75% 51%  5-GGAGCUAGACGGGUACGAGTT (SEQ ID NO: 501) TTCCUCGAUCUGCCCAUGCUC-5 (SEQ ID NO: 500) 68-3A Specific modification (2′-O-methyl) ++ 82% 9% 5-GGAGC UAGACGGG UACGAGTT (SEQ ID NO: 502) TTCCUCGAU CUGCCCAU GCUC-5 (SEQ ID NO: 503) 68-3B Specific modification (2′-O-methyl) ++ 81% 10%  5-GGAGC UA GACGGG UACGAGTT (SEQ ID NO: 504) TTCCUCGAU CUGCCCAUGCUC-5 (SEQ ID NO: 505)

TABLE 69 dog B cell lymphoma(NM_001003016) 489-507 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 69-1 Unmodified siRNA ++ 70% 0% 5-CGGGUACGAGCCGGAACCUTT (SEQ ID NO: 506) TTGCCCAUGCUCGGCCUUGGA-5 (SEQ ID NO: 507) 69-2 Random modification (2′-deoxy-2′-fluoro) +++ 61% 43%  5-CGGGUACGAGCCGGAACCUTT (SEQ ID NO: 508) TTGCCCAUGCUCGGCCUUGGA-5 (SEQ ID NO: 507) 69-3A Specific modification (2′-deoxy-2′-fluoro) +++ 68% 8% 5-CGGG UA CGAGCCGGAACCUTT (SEQ ID NO: 509) TTGCCCAU GCUCGGCCUUGGA-5 (SEQ ID NO: 510) 69-3B Specific modification (2′-deoxy-2′-fluoro) +++ 69% 1% 5-CGGGUACGAGCCGGAACCUTT (SEQ ID NO: 509) TTGCCCAU GCUCGGCCUUGGA-5 (SEQ ID NO: 511)

TABLE 70 dog B cell lymphoma(NM_001003016) 578-596 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 70-1 Unmodified siRNA + 87% 0% 5-ACGGCUCGCUACCCUCGACTT (SEQ ID NO: 512) TTUGCCGAGCGAUGGGAGCUG-5 (SEQ ID NO: 513) 70-2 Random modification (2′-deoxy-2′-fluoro) +++ 72% 37%  5-ACGGCUCGCUACCCUCGACTT (SEQ ID NO: 514) TTUGCCGAGCGAUGGGAGCUG-5 (SEQ ID NO: 513) 70-3A Specific modification (2′-deoxy-2′-fluoro) +++ 78% 4% 5-ACGGCUCGC UACCCUCGACTT (SEQ ID NO: 515) TTUGCCGAGCGAU GGGAGCUG-5 (SEQ ID NO: 516) 70-3B Specific modification (2′-deoxy-2′-fluoro) 5-ACGGCUCGCUA CCCUCGACTT +++ 83% 1% (SEQ ID NO: 517) TTUGCCGAGCGAUGGGAGCUG-5 (SEQ ID NO: 516)

TABLE 71 dog B cell lymphoma(NM_001003016) 1071-1089 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 71-1 Unmodified siRNA + 97% 0% 5-AGAGGACCUAGAAGGCGGCTT (SEQ ID NO: 518) TTUCUCCUGGAUCUUCCGCCG-5 (SEQ ID NO: 519) 71-2 Random modification (2′-O-methyl) ++ 72% 34%  5-AGAGGACCUAGAAGGCGGCTT (SEQ ID NO: 520) TTUCUCCUGGAUCUUCCGCCG-5 (SEQ ID NO: 521) 71-3A Specific modification (2′-O-methyl) ++ 89% 4% 5-AGAGGACC UAGAAGGCGGCTT (SEQ ID NO: 522) TTUCUCCUGGAU CUUCCGCCG-5 (SEQ ID NO: 523) 71-3B Specific modification (2′-O-methyl) ++ 92% 1% 5-AGAGGACCUA GAAGGCGGCTT (SEQ ID NO: 524) TTUCUCCUGGAUCUUCCGCCG-5 (SEQ ID NO: 523)

TABLE 72 dog B cell lymphoma(NM_001003016) 21-39 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 72-1 Unmodified siRNA + 77% 0% 5-AACUCUACUGUGGAGUCGGTT (SEQ ID NO: 525) TTUUGAGAUGACACCUCAGCC-5 (SEQ ID NO: 526) 72-2 Random modification (2′-O-methyl) +++ 57% 32%  5-AACUCUACUGUGGAGUCGGTT (SEQ ID NO: 527) TTUUGAGAUGACACCUCAGCC-5 (SEQ ID NO: 528) 72-3A Specific modification (2′-O-methyl) +++ 68% 8% 5-AACUC UACUGUGGAGUCGGTT (SEQ ID NO: 529) TTUUGAGAU GACACCUCAGCC-5 (SEQ ID NO: 530) 72-3B Specific modification (2′-O-methyl) +++ 69% 1% 5-AACUC UACUGUGGAGUCGGTT (SEQ ID NO: 531) TTUUGAGAU GACACCUCAGCC-5 (SEQ ID NO: 532)

TABLE 73 dog B cell lymphoma(NM_001003016) 124-142 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 73-1 Unmodified siRNA + 86% 0% 5-AGAAACGCAGUAAUCCGGATT (SEQ ID NO: 533) TTUCUUUGCGUCAUUAGGCCU-5 (SEQ ID NO: 534) 73-2 Random modification (2′-O-methyl) +++ 80% 43%  5-AGAAACGCAGUAAUCCGGATT (SEQ ID NO: 535) TTUCUUUGCGUCAUUAGGCCU-5 (SEQ ID NO: 536) 73-3A Specific modification (2′-O-methyl) ++ 81% 6% 5-AGAAACGCAG UAAUCCGGATT (SEQ ID NO: 537) TTUCUUUGCGUCAU UAGGCCU-5 (SEQ ID NO: 538) 73-3B Specific modification (2′-O-methyl) ++ 85% 1% 5-AGAAACGCAG UA AUCCGGATT (SEQ ID NO: 539) TTUCUUUGCGUCAU UAGGCCU-5 (SEQ ID NO: 540)

TABLE 74 dog B cell lymphoma(NM_001003016) 132-150 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 74-1 Unmodified siRNA + 72% 0% 5-AGUAAUCCGGACUCAACUCTT (SEQ ID NO: 541) TTUCAUUAGGCCUGAGUUGAG-5 (SEQ ID NO: 542) 74-2 Random modification (2′-deoxy-2′-fluoro) ++ 59% 17%  5-AGUAAUCCGGACUCAACUCTT (SEQ ID NO: 543) TTUCAUUAGGCCUGAGUUGAG-5 (SEQ ID NO: 542) 74-3A Specific modification (2′-deoxy-2′-fluoro) ++ 68% 4% 5-AG UAAUCCGGACUCAACUCTT (SEQ ID NO: 544) TTUCAU UAGGCCUGAGUUGAG-5 (SEQ ID NO: 545) 74-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 1% 5-AG UAAUCCGGACUCAACUCTT (SEQ ID NO: 546) TTUCAU UAGGCCUGAGUUGAG-5 (SEQ ID NO: 547)

TABLE 75 dog B cell lymphoma(NM_001003016) 616-634 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 75-1 Unmodified siRNA + 81% 0% 5-GAGGAAGAUGAGUUGUACCTT (SEQ ID NO: 548) TTCUCCUUCUACUCAACAUGG-5 (SEQ ID NO: 549) 75-2 Random modification (2′-O-methyl) ++ 70% 29%  5-GAGGAAGAUGAGUUGUACCTT (SEQ ID NO: 550) TTCUCCUUCUACUCAACAUGG-5 (SEQ ID NO: 549) 75-3A Specific modification (2′-O-methyl) +++ 76% 7% 5-GAGGAAGA UGAGUUGUACCTT (SEQ ID NO: 551) TTCUCCUUCUAC UCAACAUGG-5 (SEQ ID NO: 552) 75-3B Specific modification (2′-O-methyl) +++ 77% 2% 5-GAGGAAGA UGAGUUGUACCTT (SEQ ID NO: 553) TTCUCCUUCUAC UCAACAUGG-5 (SEQ ID NO: 554)

TABLE 76 dog B cell lymphoma(NM_001003016) 993-1011 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 76-1 Unmodified siRNA + 62% 0% 5-AGAUGUUCUCGUAAGGACGTT (SEQ ID NO: 555) TTUCUACAAGAGCAUUCCUGC-5 (SEQ ID NO: 556) 76-2 Random modification (2′-O-methyl) +++ 53% 17%  5-AGAUGUUCUCGUAAGGACGTT (SEQ ID NO: 557) TTUCUACAAGAGCAUUCCUGC-5 (SEQ ID NO: 556) 76-3A Specific modification (2′-O-methyl) +++ 60% 6% 5-AGAUGUUCUCG UAAGGACGTT (SEQ ID NO: 558) TTUCUACAAGAGCAU UCCUGC-5 (SEQ ID NO: 559) 76-3B Specific modification (2′-O-methyl) +++ 69% 1% 5-AGAUGUUCUCGUAAGGACGTT (SEQ ID NO: 555) TTUCUACAAGAGCAU UCCUGC-5 (SEQ ID NO: 560)

TABLE 77 dog B cell lymphoma(NM_001003016) 999-1017 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 77-1 Unmodified siRNA + 58% 0% 5-UCUCGUAAGGACGAAACGATT (SEQ ID NO: 561) TTAGAGCAUUCCUGCUUUGCU-5 (SEQ ID NO: 562) 77-2 Random modification (2′-O-methyl) ++ 34% 21%  5-UCUCGUAAGGACGAAACGATT (SEQ ID NO: 563) TTAGAGCAUUCCUGCUUUGCU-5 (SEQ ID NO: 562) 77-3A Specific modification (2′-O-methyl) ++ 52% 6% 5-UCUCG UA AGGACGAAACGATT (SEQ ID NO: 564) TTAGAGCAU UCCUGCUUUGCU-5 (SEQ ID NO: 565) 77-3B Specific modification (2′-O-methyl) ++ 55% 0% 5-UCUCGUAAGGACGAAACGATT (SEQ ID NO: 561) TTAGAGCAU UCCUGCUUUGCU-5 (SEQ ID NO: 566)

TABLE 78 dog B cell lymphoma(NM_001003016) 1268-1286 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 78-1 Unmodified siRNA ++ 71% 0% 5-GCUGUAACCUCGGAGAGUUTT (SEQ ID NO: 567) TTCGACAUUGGAGCCUCUCAA-5 (SEQ ID NO: 568) 78-2 Random modification (2′-deoxy-2′-fluoro) +++ 51% 23%  5-GCUGUAACCUCGGAGAGUUTT (SEQ ID NO: 569) TTCGACAUUGGAGCCUCUCAA-5 (SEQ ID NO: 568) 78-3A Specific modification (2′-deoxy-2′-fluoro) +++ 62% 4% 5-GCUG UAACCUCGGAGAGUUTT (SEQ ID NO: 570) TTCGAC AU UGGAGCCUCUCAA-5 (SEQ ID NO: 571) 78-3B Specific modification (2′-deoxy-2′-fluoro) +++ 69% 1% 5-GCUG UAACCUCGGAGAGUUTT (SEQ ID NO: 572) TTCGACAU UGGAGCCUCUCAA-5 (SEQ ID NO: 573)

TABLE 79 dog B cell lymphoma(NM_001003016) 1275-1293 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 79-1 Unmodified siRNA + 87% 0% 5-CCUCGGAGAGUUCUACUCUTT (SEQ ID NO: 574) TTGGAGCCUCUCAAGAUGAGA-5 (SEQ ID NO: 575) 79-2 Random modification (2′-O-methyl) ++ 34% 27%  5-CCUCGGAGAGUUCUACUCUTT (SEQ ID NO: 576) TTGGAGCCUCUCAAGAUGAGA-5 (SEQ ID NO: 575) 79-3A Specific modification (2′-O-methyl) ++ 85% 3% 5-CCUCGGAGAGUUC UACUCUTT (SEQ ID NO: 577) TTGGAGCCUCUCAAGAU GAGA-5 (SEQ ID NO: 578) 79-3B Specific modification (2′-O-methyl) ++ 85% 0% 5-CCUCGGAGAGUUCUACUCUTT (SEQ ID NO: 574) TTGGAGCCUCUCAAGAU GAGA-5 (SEQ ID NO: 579)

TABLE 80 dog B cell lymphoma(NM_001003016) 1308-1326 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 80-1 Unmodified siRNA + 71% 0% 5-GCAAGUGGCAAGAGGAUUATT (SEQ ID NO: 580) TTCGUUCACCGUUCUCCUAAU-5 (SEQ ID NO: 581) 80-2 Random modification (2′-O-methyl) ++ 55% 36%  5-GCAAGUGGCAAGAGGAUUATT (SEQ ID NO: 582) TTCGUUCACCGUUCUCCUAAU-5 (SEQ ID NO: 581) 80-3A Specific modification (2′-O-methyl) ++ 68% 8% 5-GCAAGUGGCAAGAGGAU UATT (SEQ ID NO: 583) TTCGUUCACCGUUCUCCUAAU -5 (SEQ ID NO: 584) 80-3B Specific modification (2′-O-methyl) ++ 69% 1% 5-GCAAGUGGCAAGAGGAU UATT (SEQ ID NO: 585) TTCGUUCACCGUUCUCCUAAU -5 (SEQ ID NO: 586)

TABLE 81 dog B cell lymphoma(NM_001003016) 1347-1365 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 81-1 Unmodified siRNA + 86% 0% 5-AUGGGAGAAGUAGUCCCCCTT (SEQ ID NO: 587) TTUACCCUCUUCAUCAGGGGG-5 (SEQ ID NO: 588) 81-2 Random modification (2′-O-methyl) +++ 71% 21%  5-AUGGGAGAAGUAGUCCCCCTT (SEQ ID NO: 589) TTUACCCUCUUCAUCAGGGGG-5 (SEQ ID NO: 588) 81-3A Specific modification (2′-O-methyl) +++ 82% 4% 5-AUGGGAGAAG UAGUCCCCCTT (SEQ ID NO: 590) TTUACCCUCUUCAU CAGGGGG-5 (SEQ ID NO: 591) 81-3B Specific modification (2′-O-methyl) +++ 84% 1% 5-AUGGGAGAAG UAGUCCCCCTT (SEQ ID NO: 592) TTUACCCUCUUCAU CAGGGGG-5 (SEQ ID NO: 593)

TABLE 82 dog B cell lymphoma(NM_001003016) 1354-1372 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 82-1 Unmodified siRNA + 75% 0% 5-AAGUAGUCCCCCUUGAAGATT (SEQ ID NO: 594) TTUUCAUCAGGGGGAACUUCU-5 (SEQ ID NO: 595) 82-2 Random modification (2′-deoxy-2′-fluoro) ++ 53% 27%  5-AAGUAGUCCCCCUUGAAGATT (SEQ ID NO: 596) TTUUCAUCAGGGGGAACUUCU-5 (SEQ ID NO: 595) 82-3A Specific modification (2′-deoxy-2′-fluoro) ++ 64% 6% 5-AAG UAGUCCCCCUUGAAGATT (SEQ ID NO: 597) TTUUCAU CAGGGGGAACUUCU-5 (SEQ ID NO: 598) 82-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 1% 5-AAGUA GUCCCCCUUGAAGATT (SEQ ID NO: 599) TTUUCAU CAGGGGGAACUUCU-5 (SEQ ID NO: 600)

TABLE 83 dog B cell lymphoma(NM_001003016) 1461-1479 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 83-1 Unmodified siRNA + 97% 0% 5-GGUAGGGUUGAAGAGACUUTT (SEQ ID NO: 601) TTCCAUCCCAACUUCUCUGAA-5 (SEQ ID NO: 602) 83-2 Random modification (2′-O-methyl) +++ 58% 27%  5-GGUAGGGUUGAAGAGACUUTT (SEQ ID NO: 603) TTCCAUCCCAACUUCUCUGAA-5 (SEQ ID NO: 604) 83-3A Specific modification (2′-O-methyl) +++ 94% 3% 5-GG UAGGGUUGAAGAGACUUTT (SEQ ID NO: 605) TTCCAU CCCAACUUCUCUGAA-5 (SEQ ID NO: 606) 83-3B Specific modification (2′-O-methyl) +++ 95% 0% 5-GGUAGGGUUGAAGAGACUUTT (SEQ ID NO: 605) TTCCAU CCCAACUUCUCUGAA-5 (SEQ ID NO: 607)

TABLE 84 623-641 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 84-1 Unmodified siRNA ++ 86% 0% 5-AGCGCUUAAAGGGCGAGAAGATT (SEQ ID NO: 609) TTUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 610) 84-2 Random modification (2′-O-methyl) +++ 49% 25%  5-AGCGCUUAAAGGGCGAGAAGATT (SEQ ID NO: 611) TTUCGCGAAUUUCCCGCUCUUCU-5 (SEQ ID NO: 610) 84-3A Specific modification (2′-O-methyl) +++ 85% 7% 5-AGCGCU UAAAGGGCGAGAAGATT (SEQ ID NO: 612) TTUCGCGAAU UUCCCGCUCUUCU-5 (SEQ ID NO: 613) 84-3B Specific modification (2′-O-methyl) 5-AGCGCU UAAAGGGCGAGAAGATT +++ 85% 1% (SEQ ID NO: 614) TTUCGCGAAU UUCCCGCUCUUCU-5 (SEQ ID NO: 615)

TABLE 85 2541-2559 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 85-1 Unmodified siRNA + 91% 0% 5-GGCCUUUCUCUCUAGAUAUTT (SEQ ID NO: 616) TTCCGGAAAGAGAGAUCUAUA-5 (SEQ ID NO: 617) 85-2 Random modification (2′-O-methyl) +++ 80% 31%  5-GGCCUUUCUCUCUAGAUAUTT (SEQ ID NO: 618) TTCCGGAAAGAGAGAUCUAUA-5 (SEQ ID NO: 617) 85-3A Specific modification (2′-O-methyl) +++ 89% 5% 5-GGCCUUUCUCUC UAGA UAUTT (SEQ ID NO: 619) TTCCGGAAAGAGAGAU CUAU A-5 (SEQ ID NO: 620) 85-3B Specific modification (2′-O-methyl) +++ 90% 1% 5-GGCCUUUCUCUCUAGAUAUTT (SEQ ID NO: 616) TTCCGGAAAGAGAGAU CUAU A-5 (SEQ ID NO: 621)

TABLE 86 2785-2803 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 86-1 Unmodified siRNA + 49% 0% 5-GCCUCUCUAUCCUUAGCUUTT (SEQ ID NO: 622) TTCGGAGAGAUAGGAAUCGAA-5 (SEQ ID NO: 623) 86-2 Random modification (2′-deoxy-2′-fluoro) +++ 34% 37%  5-GCCUCUCUAUCCUUAGCUUTT (SEQ ID NO: 624) TTCGGAGAGAUAGGAAUCGAA-5 (SEQ ID NO: 625) 86-3A Specific modification (2′-deoxy-2′-fluoro) +++ 47% 6% 5-GCCUCUC UAUCCU UAGCUUTT (SEQ ID NO: 626) TTCGGAGAGAU AGGAAU CGAA-5 (SEQ ID NO: 627) 86-3B Specific modification (2′-deoxy-2′-fluoro) +++ 48% 1% 5-GCCUCUCUAUCCUUAGCUUTT (SEQ ID NO: 622) TTCGGAGAGAU AGGAAU CGAA-5 (SEQ ID NO: 628)

TABLE 87 487-505 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 87-1 Unmodified siRNA + 90% 0% 5-AAGGACCUAGAGGAGUCACTT (SEQ ID NO: 629) TTUUCCUGGAUCUCCUCAGUG-5 (SEQ ID NO: 630) 87-2 Random modification (2′-deoxy-2′-fluoro) ++ 31% 25%  5-AAGGACCUAGAGGAGUCACTT (SEQ ID NO: 631) TTUUCCUGGAUCUCCUCAGUG-5 (SEQ ID NO: 630) 87-3A Specific modification (2′-deoxy-2′-fluoro) ++ 87% 4% 5-AAGGACC UAGAGGAGUCACTT (SEQ ID NO: 632) TTUUCCUGGAU CUCCUCAGUG-5 (SEQ ID NO: 633) 87-3B Specific modification (2′-deoxy-2′-fluoro) ++ 88% 1% 5-AAGGACC UAGAGGAGUCACTT (SEQ ID NO: 634) TTUUCCUGGAU CUCCUCAGUG-5 (SEQ ID NO: 635)

TABLE 88 614-632 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 88-1 Unmodified siRNA + 87% 0% 5-CUGACCGGAAGCGCUUAAATT (SEQ ID NO: 636) TTGACUGGCCUUCGCGAAUUU-5 (SEQ ID NO: 637) 88-2 Random modification (2′-O-methyl) +++ 27% 37%  5-CUGACCGGAAGCGCUUAAATT (SEQ ID NO: 638) TTGACUGGCCUUCGCGAAUUU-5 (SEQ ID NO: 639) 88-3A Specific modification (2′-O-methyl) +++ 85% 5% 5-CUGACCGGAAGCGCU UAAATT (SEQ ID NO: 640) TTGACUGGCCUUCGCGAAU UU-5 (SEQ ID NO: 641) 88-3B Specific modification (2′-O-methyl) +++ 86% 1% 5-CUGACCGGAAGCGCU UAAATT (SEQ ID NO: 642) TTGACUGGCCUUCGCGAAU UU-5 (SEQ ID NO: 643)

TABLE 89 628-646 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 89-1 Unmodified siRNA ++ 89% 0% 5-UUAAAGGGCGAGAAGACCGTT (SEQ ID NO: 644) TTAAUUUCCCGCUCUUCUGGC-5 (SEQ ID NO: 645) 89-2 Random modification (2′-O-methyl) +++ 67% 47%  5-UUAAAGGGCGAGAAGACCGTT (SEQ ID NO: 646) TTAAUUUCCCGCUCUUCUGGC-5 (SEQ ID NO: 645) 89-3A Specific modification (2′-O-methyl) +++ 85% 3% 5-U UA AAGGGCGAGAAGACCGTT (SEQ ID NO: 647) TTAAU UUCCCGCUCUUCUGGC-5 (SEQ ID NO: 648) 89-3B Specific modification (2′-O-methyl) +++ 87% 0% 5-U UAAAGGGCGAGAAGACCGTT (SEQ ID NO: 649) TTAAU UUCCCGCUCUUCUGGC-5 (SEQ ID NO: 650)

TABLE 90 1257-1275 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 90-1 Unmodified siRNA + 77% 0% 5-GAAGAGCCUACACAACCCUTT (SEQ ID NO: 651) TTCUUCUCGGAUGUGUUGGGA-5 (SEQ ID NO: 652) 90-2 Random modification (2′-O-methyl) ++ 50% 27%  5-GAAGAGCCUACACAACCCUTT (SEQ ID NO: 653) TTCUUCUCGGAUGUGUUGGGA-5 (SEQ ID NO: 654) 90-3A Specific modification (2′-O-methyl) ++ 75% 5% 5-GAAGAGCC UA CACAACCCUTT (SEQ ID NO: 655) TTCUUCUCGGAU GUGUUGGGA-5 (SEQ ID NO: 656) 90-3B Specific modification (2′-O-methyl) ++ 76% 1% 5-GAAGAGCC UA CACAACCCUTT (SEQ ID NO: 657) TTCUUCUCGGAU GUGUUGGGA-5 (SEQ ID NO: 658)

TABLE 91 1288-1306 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 91-1 Unmodified siRNA + 83% 0% 5-CUAGAGGAUCUUGAAGACCTT (SEQ ID NO: 659) TTGAUCUCCUAGAACUUCUGG-5 (SEQ ID NO: 660) 91-2 Random modification (2′-deoxy-2′-fluoro) ++ 61% 25%  5-CUAGAGGAUCUUGAAGACCTT (SEQ ID NO: 661) TTGAUCUCCUAGAACUUCUGG-5 (SEQ ID NO: 660) 91-3A Specific modification (2′-deoxy-2′-fluoro) ++ 78% 6% 5-C UAGAGGAUCUUGAAGACCTT (SEQ ID NO: 662) TTGAU CUCCUAGAACUUCUGG-5 (SEQ ID NO: 663) 91-3B Specific modification (2′-deoxy-2′-fluoro) ++ 81% 1% 5-C UAGAGGAUCUUGAAGACCTT (SEQ ID NO: 664) TTGAUCUCCUAGAACUUCUGG-5 (SEQ ID NO: 660)

TABLE 92 1427-1445 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 92-1 Unmodified siRNA + 91% 0% 5-ACAUAGAGGAAGACGCGGATT (SEQ ID NO: 665) TTUGUAUCUCCUUCUGCGCCU-5 (SEQ ID NO: 666) 92-2 Random modification (2′-deoxy-2′-fluoro) +++ 57% 34%  5-ACAUAGAGGAAGACGCGGATT (SEQ ID NO: 667) TTUGUAUCUCCUUCUGCGCCU-5 (SEQ ID NO: 668) 92-3A Specific modification (2′-deoxy-2′-fluoro) +++ 86% 6% 5-ACA UAGAGGAAGACGCGGATT (SEQ ID NO: 669) TTUGU AU CUCCUUCUGCGCCU-5 (SEQ ID NO: 670) 92-3B Specific modification (2′-deoxy-2′-fluoro) +++ 89% 0% 5-ACAUAGAGGAAGACGCGGATT (SEQ ID NO: 669) TTUGUAU CUCCUUCUGCGCCU-5 (SEQ ID NO: 671)

TABLE 93 2091-2109 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 93-1 Unmodified siRNA + 50% 0% 5-AUCGUCGUCAGGGUAAGGUTT (SEQ ID NO: 672) TTUAGCAGCAGUCCCAUUCCA-5 (SEQ ID NO: 673) 93-2 Random modification (2′-O-methyl) ++ 34% 37%  5-AUCGUCGUCAGGGUAAGGUTT (SEQ ID NO: 674) TTUAGCAGCAGUCCCAUUCCA-5 (SEQ ID NO: 675) 93-3A Specific modification (2′-O-methyl) ++ 47% 4% 5-AUCGUCGUCAGGG UAAGGUTT (SEQ ID NO: 676) TTUAGCAGCAGUCCCAU UCCA-5 (SEQ ID NO: 677) 93-3B Specific modification (2′-O-methyl) ++ 49% 1% 5-AUCGUCGUCAGGG UAAGGUTT (SEQ ID NO: 678) TTUAGCAGCAGUCCCAU UCCA-5 (SEQ ID NO: 679)

TABLE 94 2537-2555 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 94-1 Unmodified siRNA + 48% 0% 5-CUCUGGCCUUUCUCUCUAGTT (SEQ ID NO: 680) TTGAGACCGGAAAGAGAGAUC-5 (SEQ ID NO: 681) 94-2 Random modification (2′-O-methyl) ++ 24% 22%  5-CUCUGGCCUUUCUCUCUAGTT (SEQ ID NO: 682) TTGAGACCGGAAAGAGAGAUC-5 (SEQ ID NO: 681) 94-3A Specific modification (2′-O-methyl) ++ 45% 5% 5-CUCUGGCCUUUCUCUC UAGTT (SEQ ID NO: 683) TTGAGACCGGAAAGAGAGAUC-5 (SEQ ID NO: 684) 94-3B Specific modification (2′-O-methyl) ++ 47% 1% 5-CUCUGGCCUUUCUCUC UAGTT (SEQ ID NO: 685) TTGAGACCGGAAAGAGAGAUC-5 (SEQ ID NO: 681)

TABLE 95 2688-2706 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 95-1 Unmodified siRNA + 73% 0% 5-GACAAGGGAAGGUUAGCCUTT (SEQ ID NO: 686) TTCUGUUCCCUUCCAAUCGGA-5 (SEQ ID NO: 687) 95-2 Random modification (2′-O-methyl) +++ 34% 29%  5-GACAAGGGAAGGUUAGCCUTT (SEQ ID NO: 688) TTCUGUUCCCUUCCAAUCGGA-5 (SEQ ID NO: 687) 95-3A Specific modification (2′-O-methyl) +++ 68% 6% 5-GACAAGGGAAGGU UAGCCUTT (SEQ ID NO: 689) TTCUGUUCCCUUCCAAU CGGA-5 (SEQ ID NO: 690) 95-3B Specific modification (2′-O-methyl) +++ 72% 1% 5-GACAAGGGAAGGU UAGCCUTT (SEQ ID NO: 691) TTCUGUUCCCUUCCAAU CGGA-5 (SEQ ID NO: 692)

TABLE 96 2988-2006 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 96-1 Unmodified siRNA + 48% 0% 5-AGACUAAGCCCAAAAGGGCTT (SEQ ID NO: 693) TTUCUGAUUCGGGUUUUCCCG-5 (SEQ ID NO: 694) 96-2 Random modification (2′-deoxy-2′-fluoro) +++ 26% 21%  5-AGACUAAGCCCAAAAGGGCTT (SEQ ID NO: 695) TTUCUGAUUCGGGUUUUCCCG-5 (SEQ ID NO: 694) 96-3A Specific modification (2′-deoxy-2′-fluoro) +++ 45% 5% 5-AGAC UAAGCCCAAAAGGGCTT (SEQ ID NO: 696) TTUCUGAU UCGGGUUUUCCCG-5 (SEQ ID NO: 697) 96-3B Specific modification (2′-deoxy-2′-fluoro) +++ 47% 1% 5-AGAC UAAGCCCAAAAGGGCTT (SEQ ID NO: 698) TTUCUGAU UCGGGUUUUCCCG-5 (SEQ ID NO: 699)

TABLE 97 3132-3150 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 97-1 Unmodified siRNA + 81% 0% 5-CCUCCCCAUCCCCUUUUAATT (SEQ ID NO: 700) TTGGAGGGGUAGGGGAAAAUU-5 (SEQ ID NO: 701) 97-2 Random modification (2′-O-methyl) ++ 48% 44%  5-CCUCCCCAUCCCCUUUUAATT (SEQ ID NO: 702) TTGGAGGGGUAGGGGAAAAUU-5 (SEQ ID NO: 703) 97-3A Specific modification (2′-O-methyl) ++ 80% 4% 5-CCUCCCCAUCCCCUUU UAATT (SEQ ID NO: 704) TTGGAGGGGUAGGGGAAA AUU-5 (SEQ ID NO: 705) 97-3B Specific modification (2′-O-methyl) ++ 80% 0% 5-CCUCCCCAUCCCCUUUUAATT (SEQ ID NO: 700) TTGGAGGGGUAGGGGAAA AUU-5 (SEQ ID NO: 706)

TABLE 98 3471-3489 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 98-1 Unmodified siRNA + 73% 0% 5-AUCAGAGGGAGGUCUUAGATT (SEQ ID NO: 707) TTUAGUCUCCCUCCAGAAUCU-5 (SEQ ID NO: 708) 98-2 Random modification (2′-O-methyl) ++ 19% 32%  5-AUCAGAGGGAGGUCUUAGATT (SEQ ID NO: 709) TTUAGUCUCCCUCCAGAAUCU-5 (SEQ ID NO: 710) 98-3A Specific modification (2′-O-methyl) ++ 68% 6% 5-AUCAGAGGGAGGUCU UAGATT (SEQ ID NO: 711) TTUAGUCUCCCUCCAGAAU CU-5 (SEQ ID NO: 712) 98-3B Specific modification (2′-O-methyl) ++ 69% 1% 5-AUCAGAGGGAGGUCU UAGATT (SEQ ID NO: 713) TTUAGUCUCCCUCCAGAAU CU-5 (SEQ ID NO: 714)

TABLE 99 3477-3495 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 99-1 Unmodified siRNA + 84% 0% 5-GGGAGGUCUUAGAAAACACTT (SEQ ID NO: 715) TTCCCUCCAGAAUCUUUUGUG-5 (SEQ ID NO: 716) 99-2 Random modification (2′-O-methyl) ++ 17% 31%  5-GGGAGGUCUUAGAAAACACTT (SEQ ID NO: 717) TTCCCUCCAGAAUCUUUUGUG-5 (SEQ ID NO: 716) 99-3A Specific modification (2′-O-methyl) ++ 84% 3% 5-GGGAGGUCU UAGAAAACACTT (SEQ ID NO: 718) TTCCCUCCAGAAU CUUUUGUG-5 (SEQ ID NO: 719) 99-3B Specific modification (2′-O-methyl) ++ 82% 0% 5-GGGAGGUCUUAGAAAACACTT (SEQ ID NO: 715) TTCCCUCCAGAAU CUUUUGUG-5 (SEQ ID NO: 720)

TABLE 100 3613-3631 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 100-1 Unmodified siRNA + 71% 0% 5-GGCUUAGUCACUCCUCUUCTT (SEQ ID NO: 721) TTCCGAAUCAGUGAGGAGAAG-5 (SEQ ID NO: 722) 100-2 Random modification (2′-deoxy-2′-fluoro) ++ 23% 14%  5-GGCUUAGUCACUCCUCUUCTT (SEQ ID NO: 723) TTCCGAAUCAGUGAGGAGAAG-5 (SEQ ID NO: 722) 100-3A Specific modification (2′-deoxy-2′-fluoro) ++ 68% 4% 5-GGCU UAGUCACUCCUCUUCTT (SEQ ID NO: 724) TTCCGAAU CAGUGAGGAGAAG-5 (SEQ ID NO: 725) 100-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 1% 5-GGCU UAGUCACUCCUCUUCTT (SEQ ID NO: 726) TTCCGAAU CAGUGAGGAGAAG-5 (SEQ ID NO: 727)

TABLE 101 Rat BIRC5(NM_022274) 42-60 BP (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 101-1 Unmodified siRNA + 77% 0% 5-ACCUUAAGGACCACCGGAUTT (SEQ ID NO: 729) TTUGGAAUUCCUGGUGGCCUA-5 (SEQ ID NO: 730) 101-2 Random modification (2′-O-methyl) ++ 52% 24%  5-ACCUUAAGGACCACCGGAUTT (SEQ ID NO: 731) TTUGGAAUUCCUGGUGGCCUA-5 (SEQ ID NO: 732) 101-3A Specific modification (2′-O-methyl) ++ 72% 6% 5-ACCU UAAGGACCACCGGAUTT (SEQ ID NO: 733) TTUGGAAU UCCUGGUGGCCUA-5 (SEQ ID NO: 734) 101-3B Specific modification (2′-O-methyl) ++ 74% 1% 5-ACCU UAAGGACCACCGGAUTT (SEQ ID NO: 735) TTUGGAAU UCCUGGUGGCCUA-5 (SEQ ID NO: 736)

TABLE 102 Rat BIRC5(NM_022274) 56-74 BP (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 102-1 Unmodified siRNA + 73% 0% 5-CGGAUCUACACCUUCAAGATT (SEQ ID NO: 737) TTGCCUAGAUGUGGAAGUUCU-5 (SEQ ID NO: 738) 102-2 Random modification (2′-O-methyl) ++ 46% 19%  5-CGGAUCUACACCUUCAAGATT (SEQ ID NO: 739) TTGCCUAGAUGUGGAAGUUCU-5 (SEQ ID NO: 740) 102-3A Specific modification (2′-O-methyl) ++ 68% 5% 5-CGGAUC UA CACCUUCAAGATT (SEQ ID NO: 741) TTGCCUAGAU GUGGAAGUUCU-5 (SEQ ID NO: 742) 102-3B Specific modification (2′-O-methyl) ++ 69% 1% 5-CGGAUC UACACCUUCAAGATT (SEQ ID NO: 743) TTGCCUAGAU GUGGAAGUUCU-5 (SEQ ID NO: 744)

TABLE 103 Rat BIRC5(NM_022274) 145-163 BP (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 103-1 Unmodified siRNA + 57% 0% 5-UACCGAGAAUGAGCCUGAUTT (SEQ ID NO: 745) TTAUGGCUCUUACUCGGACUA-5 (SEQ ID NO: 746) 103-2 Random modification (2′-O-methyl) +++ 23% 27%  5-UACCGAGAAUGAGCCUGAUTT (SEQ ID NO: 747) TTAUGGCUCUUACUCGGACUA-5 (SEQ ID NO: 748) 103-3A Specific modification (2′-O-methyl) +++ 54% 6% 5- UACCGAGAAUGAGCCUGAUTT (SEQ ID NO: 749) TTAU GGCUCUUACUCGGACUA-5 (SEQ ID NO: 750) 103-3B Specific modification (2′-O-methyl) +++ 55% 1% 5- UACCGAGAAUGAGCCUGAUTT (SEQ ID NO: 751) TTAU GGCUCUUACUCGGACUA-5 (SEQ ID NO: 752)

TABLE 104 Rat BIRC5(NM_022274) 183-201 BP (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 104-1 Unmodified siRNA + 38% 0% 5-GCUUUAAGGAACUGGAAGGTT (SEQ ID NO: 753) TTCGAAAUUCCUUGACCUUCC-5 (SEQ ID NO: 754) 104-2 Random modification (2′-O-methyl) ++ 25% 19%  5-GCUUUAAGGAACUGGAAGGTT (SEQ ID NO: 755) TTCGAAAUUCCUUGACCUUCC-5 (SEQ ID NO: 756) 104-3A Specific modification (2′-O-methyl) ++ 37% 3% 5-GCUU UAAGGAACUGGAAGGTT (SEQ ID NO: 757) TTCGAAAU UCCUUGACCUUCC-5 (SEQ ID NO: 758) 104-3B Specific modification (2′-O-methyl) ++ 37% 0% 5-GCUUUAAGGAACUGGAAGGTT (SEQ ID NO: 753) TTCGAAAU UCCUUGACCUUCC-5 (SEQ ID NO: 759)

TABLE 105 247-265 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 105-1 Unmodified siRNA + 86% 0% 5-UCCUCGUCGUCUGUUCUAATT (SEQ ID NO: 760) TTAGGAGCAGCAGACAAGAUU-5 (SEQ ID NO: 761) 105-2 Random modification (2′-O-methyl) +++ 63% 35%  5-UCCUCGUCGUCUGUUCUAATT (SEQ ID NO: 762) TTAGGAGCAGCAGACAAGAUU-5 (SEQ ID NO: 763) 105-3A Specific modification (2′-O-methyl) +++ 82% 4% 5-UCCUCGUCGUCUGUUC UAATT (SEQ ID NO: 764) TTAGGAGCAGCAGACAAGAU U-5 (SEQ ID NO: 765) 105-3B Specific modification (2′-O-methyl) +++ 84% 1% 5-UCCUCGUCGUCUGUUC UAATT (SEQ ID NO: 766) TTAGGAGCAGCAGACAAGAU U-5 (SEQ ID NO: 767)

TABLE 106 260-278 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 106-1 Unmodified siRNA ++ 73% 0% 5-UUCUAACCGGGCAGCUUCUTT (SEQ ID NO: 768) TTAAGAUUGGCCCGUCGAAGA-5 (SEQ ID NO: 769) 106-2 Random modification (2′-deoxy-2′-fluoro) +++ 61% 37%  5-UUCUAACCGGGCAGCUUCUTT (SEQ ID NO: 770) TTAAGAUUGGCCCGUCGAAGA-5 (SEQ ID NO: 769) 106-3A Specific modification (2′-deoxy-2′-fluoro) +++ 71% 5% 5-UUC UAACCGGGCAGCUUCUTT (SEQ ID NO: 771) TTAAGAU UGGCCCGUCGAAGA-5 (SEQ ID NO: 772) 106-3B Specific modification (2′-deoxy-2′-fluoro) +++ 72% 1% 5-UUC UAACCGGGCAGCUUCUTT (SEQ ID NO: 773) TTAAGAU UGGCCCGUCGAAGA-5 (SEQ ID NO: 774)

TABLE 107 920-938 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 107-1 Unmodified siRNA + 95% 0% 5-GAGGAUGGAUUCGACUUAGTT (SEQ ID NO: 775) TTCUCCUACCUAAGCUGAAUC-5 (SEQ ID NO: 776) 107-2 Random modification (2′-O-methyl) ++ 23% 22%  5-GAGGAUGGAUUCGACUUAGTT (SEQ ID NO: 777) TTCUCCUACCUAAGCUGAAUC-5 (SEQ ID NO: 778) 107-3A Specific modification (2′-O-methyl) ++ 91% 6% 5-GAGGAUGGAUUCGACU UAGTT (SEQ ID NO: 779) TTCUCCUACCUAAGCUGAAU C-5 (SEQ ID NO: 780) 107-3B Specific modification (2′-O-methyl) ++ 94% 0% 5-GAGGAUGGAUUCGACUUAGTT (SEQ ID NO: 775) TTCUCCUACCUAAGCUGAAU C-5 (SEQ ID NO: 781)

TABLE 108 1240-1258 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 108-1 Unmodified siRNA + 67% 0% 5-UAAAGCUGGAAAGGGACGGTT (SEQ ID NO: 782) TTAUUUCGACCUUUCCCUGCC-5 (SEQ ID NO: 783) 108-2 Random modification (2′-O-methyl) ++ 29% 28%  5-UAAAGCUGGAAAGGGACGGTT (SEQ ID NO: 784) TTAUUUCGACCUUUCCCUGCC-5 (SEQ ID NO: 785) 108-3A Specific modification (2′-O-methyl) ++ 65% 4% 5- UAAAGCUGGAAAGGGACGGTT (SEQ ID NO: 786) TTAU UUCGACCUUUCCCUGCC-5 (SEQ ID NO: 787) 108-3B Specific modification (2′-O-methyl) ++ 67% 1% 5- UAAAGCUGGAAAGGGACGGTT (SEQ ID NO: 788) TTAU UUCGACCUUUCCCUGCC-5 (SEQ ID NO: 789)

TABLE 109 1336-1354 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 109-1 Unmodified siRNA + 45% 0% 5-GGAAGUAAGGACCAGAGACTT (SEQ ID NO: 790) TTCCUUCAUUCCUGGUCUCUG-5 (SEQ ID NO: 791) 109-2 Random modification (2′-O-methyl) ++ 23% 27%  5-GGAAGUAAGGACCAGAGACTT (SEQ ID NO: 792) TTCCUUCAUUCCUGGUCUCUG-5 (SEQ ID NO: 793) 109-3A Specific modification (2′-O-methyl) ++ 41% 4% 5-GGAAG UAAGGACCAGAGACTT (SEQ ID NO: 794) TTCCUUCAU UCCUGGUCUCUG-5 (SEQ ID NO: 795) 109-3B Specific modification (2′-O-methyl) ++ 44% 1% 5-GGAAG UAAGGACCAGAGACTT (SEQ ID NO: 796) TTCCUUCAU UCCUGGUCUCUG-5 (SEQ ID NO: 797)

TABLE 110 1862-1880 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 110-1 Unmodified siRNA ++ 70% 0% 5-AAGGCCAACCGAUACUUCUTT (SEQ ID NO: 798) TTUUCCGGUUGGCUAUGAAGA-5 (SEQ ID NO: 799) 110-2 Random modification (2′-deoxy-2′-fluoro) +++ 46% 24%  5-AAGGCCAACCGAUACUUCUTT (SEQ ID NO: 800) TTUUCCGGUUGGCUAUGAAGA-5 (SEQ ID NO: 801) 110-3A Specific modification (2′-deoxy-2′-fluoro) +++ 68% 5% 5-AAGGCCAACCGA UACUUCUTT (SEQ ID NO: 802) TTUUCCGGUUGGCUAU GAAGA-5 (SEQ ID NO: 803) 110-3B Specific modification (2′-deoxy-2′-fluoro) +++ 69% 1% 5-AAGGCCAACCGA UACUUCUTT (SEQ ID NO: 804) TTUUCCGGUUGGCUAU GAAGA-5 (SEQ ID NO: 805)

TABLE 111 2489-2507 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 111-1 Unmodified siRNA + 67% 0% 5-GUUCACGUCCUACCCCUUUTT (SEQ ID NO: 806) TTCAAGUGCAGGAUGGGGAAA-5 (SEQ ID NO: 807) 111-2 Random modification (2′-deoxy-2′-fluoro) ++ 23% 27%  5-GUUCACGUCCUACCCCUUUTT (SEQ ID NO: 808) TTCAAGUGCAGGAUGGGGAAA-5 (SEQ ID NO: 809) 111-3A Specific modification (2′-deoxy-2′-fluoro) ++ 65% 5% 5-GUUCACGUCC UACCCCUUUTT (SEQ ID NO: 810) TTCAAGUGCAGGAU GGGGAAA-5 (SEQ ID NO: 811) 111-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 0% 5-GUUCACGUCCUACCCCUUUTT (SEQ ID NO: 806) TTCAAGUGCAGGAU GGGGAAA-5 (SEQ ID NO: 812)

TABLE 112 3572-3590 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 112-1 Unmodified siRNA + 71% 0% 5-AGAGUUGGGAUUAGGGCUUTT (SEQ ID NO: 813) TTUCUCAACCCUAAUCCCGAA-5 (SEQ ID NO: 814) 112-2 Random modification (2′-O-methyl) ++ 45% 19%  5-AGAGUUGGGAUUAGGGCUUTT (SEQ ID NO: 815) TTUCUCAACCCUAAUCCCGAA-5 (SEQ ID NO: 816) 112-3A Specific modification (2′-O-methyl) ++ 68% 4% 5-AGAGUUGGGAU UAGGGCUUTT (SEQ ID NO: 817) TTUCUCAACCCUAAU CCCGAA-5 (SEQ ID NO: 818) 112-3B Specific modification (2′-O-methyl) ++ 69% 0% 5-AGAGUUGGGAUUAGGGCUUTT (SEQ ID NO: 819) TTUCUCAACCCUAAU CCCGAA-5 (SEQ ID NO: 820)

TABLE 113 3694-3712 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 113-1 Unmodified siRNA + 81% 0% 5-UUACAAAGGAUCUCCUCCCTT (SEQ ID NO: 821) TTAAUGUUUCCUAGAGGAGGG-5 (SEQ ID NO: 822) 113-2 Random modification (2′-O-methyl) ++ 57% 31%  5-UUACAAAGGAUCUCCUCCCTT (SEQ ID NO: 823) TTAAUGUUUCCUAGAGGAGGG-5 (SEQ ID NO: 824) 113-3A Specific modification (2′-O-methyl) ++ 78% 5% 5-U UA CAAAGGAUCUCCUCCCTT (SEQ ID NO: 825) TTAAU GUUUCCUAGAGGAGGG-5 (SEQ ID NO: 826) 113-3B Specific modification (2′-O-methyl) ++ 69% 1% 5-U UACAAAGGAUCUCCUCCCTT (SEQ ID NO: 827) TTAAU GUUUCCUAGAGGAGGG-5 (SEQ ID NO: 828)

TABLE 114 5159-5177 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 114-1 Unmodified siRNA + 70% 0% 5-AACAGCCUUACCCCGAUUCTT (SEQ ID NO: 829) TTUUGUCGGAAUGGGGCUAAG-5 (SEQ ID NO: 830) 114-2 Random modification (2′-O-methyl) ++ 32% 24%  5-AACAGCCUUACCCCGAUUCTT (SEQ ID NO: 831) TTUUGUCGGAAUGGGGCUAAG-5 (SEQ ID NO: 832) 114-3A Specific modification (2′-O-methyl) ++ 68% 4% 5-AACAGCCU UACCCCGAUUCTT (SEQ ID NO: 833) TTUUGUCGGAAU GGGGCUAAG-5 (SEQ ID NO: 834) 114-3B Specific modification (2′-O-methyl) ++ 69% 0% 5-AACAGCCUUACCCCGAUUCTT (SEQ ID NO: 829) TTUUGUCGGAAU GGGGCUAAG-5 (SEQ ID NO: 835)

TABLE 115 5166-5184 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 115-1 Unmodified siRNA + 84% 0% 5-UUACCCCGAUUCAGCCUCUTT (SEQ ID NO: 836) TTAAUGGGGCUAAGUCGGAGA-5 (SEQ ID NO: 837) 115-2 Random modification (2′-deoxy-2′-fluoro) ++ 67% 24%  5-UUACCCCGAUUCAGCCUCUTT (SEQ ID NO: 838) TTAAUGGGGCUAAGUCGGAGA-5 (SEQ ID NO: 837) 115-3A Specific modification (2′-deoxy-2′-fluoro) ++ 82% 3% 5-U UACCCCGAUUCAGCCUCUTT (SEQ ID NO: 839) TTAAU GGGGCUAAGUCGGAGA-5 (SEQ ID NO: 840) 115-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 1% 5-U UACCCCGAUUCAGCCUCUTT (SEQ ID NO: 841) TTA AUGGGGCUAAGUCGGAGA-5 (SEQ ID NO: 842)

TABLE 116 5695-5713 BP mice(NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 116-1 Unmodified siRNA + 75% 0% 5-UAACCCCAAGAACGGGCUUTT (SEQ ID NO: 843) TTAUUGGGGUUCUUGCCCGAA-5 (SEQ ID NO: 844) 116-2 Random modification (2′-deoxy-2′-fluoro) ++ 47% 25%  5-UAACCCCAAGAACGGGCUUTT (SEQ ID NO: 845) TTAUUGGGGUUCUUGCCCGAA-5 (SEQ ID NO: 846) 116-3A Specific modification (2′-deoxy-2′-fluoro) ++ 72% 6% 5- UAACCCCAAGAACGGGCUUTT (SEQ ID NO: 847) TTAU UGGGGUUCUUGCCCGAA-5 (SEQ ID NO: 848) 116-3B Specific modification (2′-deoxy-2′-fluoro) ++ 73% 1% 5- UAACCCCAAGAACGGGCUUTT (SEQ ID NO: 849) TTAU UGGGGUUCUUGCCCGAA-5 (SEQ ID NO: 850)

TABLE 117 aspergillus AF293 protein(XM_748400) 499-517 BP (SEQ ID NO: 851) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 117-1 Unmodified siRNA + 57% 0% 5-CUAGUCGAAAGAAAACGGGTT (SEQ ID NO: 852) TTGAUCAGCUUUCUUUUGCCC-5 (SEQ ID NO: 853) 117-2 Random modification (2′-O-methyl) ++ 23% 19%  5-CUAGUCGAAAGAAAACGGGTT (SEQ ID NO: 854) TTGAUCAGCUUUCUUUUGCCC-5 (SEQ ID NO: 855) 117-3A Specific modification (2′-O-methyl) ++ 55% 6% 5-C UAGUCGAAAGAAAACGGGTT (SEQ ID NO: 856) TTGAU CAGCUUUCUUUUGCCC-5 (SEQ ID NO: 857) 117-3B Specific modification (2′-O-methyl) ++ 56% 1% 5-C UAGUCGAAAGAAAACGGGTT (SEQ ID NO: 858) TTGAU CAGCUUUCUUUUGCCC-5 (SEQ ID NO: 859)

TABLE 118 aspergillus AF293 protein(XM_748400) 1214-1232 BP (SEQ ID NO: 851) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 118-1 Unmodified siRNA + 46% 0% 5-AGGACGGUACUUUCGAAAGTT (SEQ ID NO: 860) TTUCCUGCCAUGAAAGCUUUC-5 (SEQ ID NO: 861) 118-2 Random modification (2′-O-methyl) ++ 17% 51%  5-AGGACGGUACUUUCGAAAGTT (SEQ ID NO: 862) TTUCCUGCCAUGAAAGCUUUC-5 (SEQ ID NO: 863) 118-3A Specific modification (2′-O-methyl) ++ 44% 6% 5-AGGACGG UACUUUCGAAAGTT (SEQ ID NO: 864) TTUCCUGCCAU GAAAGCUUUC-5 (SEQ ID NO: 865) 118-3B Specific modification (2′-O-methyl) ++ 46% 0% 5-AGGACGGUACUUUCGAAAGTT (SEQ ID NO: 860) TTUCCUGCC AUGAAAGCUUUC-5 (SEQ ID NO: 866)

TABLE 119 Aspergillus AF293 protein XM_748400) 1234-1252 BP (SEQ ID NO: 851) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 119-1 Unmodified siRNA + 97% 0% 5-GUAUCCGAAGACGAAGCUATT (SEQ ID NO: 867) TTCAUAGGCUUCUGCUUCGAU-5 (SEQ ID NO: 868) 119-2 Random modification (2′-O-methyl) +++ 30% 31%  5-GUAUCCGAAGACGAAGCUATT (SEQ ID NO: 869) TTCAUAGGCUUCUGCUUCGAU-5 (SEQ ID NO: 870) 119-3A Specific modification (2′-O-methyl) +++ 92% 8% 5-G UAUCCGAAGACGAAGC UATT (SEQ ID NO: 871) TTCAU AGGCUUCUGCUUCGAU -5 (SEQ ID NO: 872) 119-3B Specific modification (2′-O-methyl) +++ 95% 1% 5-GUAUCCGAAGACGAAGC UATT (SEQ ID NO: 873) TTCAU AGGCUUCUGCUUCGAU -5 (SEQ ID NO: 874)

TABLE 120 Aspergillus AF293 protein(XM_748400) 14-32 BP (SEQ ID NO: 851) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 120-1 Unmodified siRNA + 91% 0% 5-AGAGAGGUGGAGGUAUCUCTT (SEQ ID NO: 875) TTUCUCUCCACCUCCAUAGAG-5 (SEQ ID NO: 876) 120-2 Random modification (2′-O-methyl) ++ 67% 24%  5-AGAGAGGUGGAGGUAUCUCTT (SEQ ID NO: 877) TTUCUCUCCACCUCCAUAGAG-5 (SEQ ID NO: 878) 120-3A Specific modification (2′-O-methyl) ++ 87% 8% 5-AGAGAGGUGGAGG UAUCUCTT (SEQ ID NO: 879) TTUCUCUCCACCUCCAU AGAG-5 (SEQ ID NO: 880) 120-3B Specific modification (2′-O-methyl) ++ 90% 1% 5-AGAGAGGUGGAGG UAUCUCTT (SEQ ID NO: 881) TTUCUCUCCACCUCCAU AGAG-5 (SEQ ID NO: 882)

TABLE 121 Aspergillus AF293 protein XM_748400) 103-121 BP (SEQ ID NO: 851) Locus Expression gene SIRNA Stability inhibition ratio Growth inhibition ratio 121-1 Unmodified siRNA + 58% 0% 5-GAAAACGCUUGUAAAGCCGTT (SEQ ID NO: 883) TTCUUUUGCGAACAUUUCGGC-5 (SEQ ID NO: 884) 121-2 Random modification (2′-O-methyl) ++ 23% 24%  5-GAAAACGCUUGUAAAGCCGTT (SEQ ID NO: 885) TTCUUUUGCGAACAUUUCGGC-5 (SEQ ID NO: 886) 121-3A Specific modification (2′-O-methyl) ++ 54% 5% 5-GAAAACGCUUG UAAAGCCGTT (SEQ ID NO: 887) TTCUUUUGCGAAC AU UUCGGC-5 (SEQ ID NO: 888) 121-3B Specific modification (2′-O-methyl) ++ 56% 0% 5-GAAAACGCUUGUAAAGCCGTT (SEQ ID NO: 883) TTCUUUUGCGAACAU UUCGGC-5 (SEQ ID NO: 889)

TABLE 122 Aspergillus AF293 protein(XM_748400) 493-511 BP (SEQ ID NO: 851) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 122-1 Unmodified siRNA + 81% 0% 5-GCUGAACUAGUCGAAAGAATT (SEQ ID NO: 890) TTCGACUUGAUCAGCUUUCUU-5 (SEQ ID NO: 891) 122-2 Random modification (2′-deoxy-2′-fluoro) ++ 49% 29%  5-GCUGAACUAGUCGAAAGAATT (SEQ ID NO: 892) TTCGACUUGAUCAGCUUUCUU-5 (SEQ ID NO: 893) 122-3A Specific modification (2′-deoxy-2′-fluoro) ++ 78% 3% 5-GCUGAAC UAGUCGAAAGAATT (SEQ ID NO: 894) TTCGACUUGAU CAGCUUUCUU-5 (SEQ ID NO: 895) 122-3B Specific modification (2′-deoxy-2′-fluoro) ++ 79% 1% 5-GCUGAAC UAGUCGAAAGAATT (SEQ ID NO: 896) TTCGACUUGAU CAGCUUUCUU-5 (SEQ ID NO: 897)

TABLE 123 Aspergillus AF293 protein(XM_748400) 537-555 BP (SEQ ID NO: 851) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 123-1 Unmodified siRNA + 38% 0% 5-GGAAGAAGAUAGAGCAUCCTT (SEQ ID NO: 898) TTCCUUCUUCUAUCUCGUAGG-5 (SEQ ID NO: 899) 123-2 Random modification (2′-deoxy-2′-fluoro) ++ 13% 19   5-GGAAGAAGAUAGAGCAUCCTT (SEQ ID NO: 900) TTCCUUCUUCUAUCUCGUAGG-5 (SEQ ID NO: 901) 123-3A Specific modification (2′-deoxy-2′-fluoro) ++ 37% 4% 5-GGAAGAAGA UAGAGCAUCCTT (SEQ ID NO: 902) TTCCUUCUUCUAU CUCGUAGG-5 (SEQ ID NO: 903) 123-3B Specific modification (2′-deoxy-2′-fluoro) ++ 37% 0% 5-GGAAGAAGAUAGAGCAUCCTT (SEQ ID NO: 898) TTCCUUCUUCUAU CUCGUAGG-5 (SEQ ID NO: 904)

TABLE 124 Aspergillus AF293 protein XM_748400) 623-641 BP (SEQ ID NO: 851) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 124-1 Unmodified siRNA + 79% 0% 5-AUCUACCCAGCUCUCCCUUTT (SEQ ID NO: 905) TTUAGAUGGGUCGAGAGGGAA-5 (SEQ ID NO: 906) 124-2 Random modification (2′-O-methyl) ++ 43% 21%  5-AUCUACCCAGCUCUCCCUUTT (SEQ ID NO: 907) TTUAGAUGGGUCGAGAGGGAA-5 (SEQ ID NO: 908) 124-3A Specific modification (2′-O-methyl) ++ 75% 6% 5-AUC UACCCAGCUCUCCCUUTT (SEQ ID NO: 909) TTUAGAU GGGUCGAGAGGGAA-5 (SEQ ID NO: 910) 124-3B Specific modification (2′-O-methyl) ++ 77% 1% 5-AUC UACCCAGCUCUCCCUUTT (SEQ ID NO: 911) TTUAGAU GGGUCGAGAGGGAA-5 (SEQ ID NO: 912)

TABLE 125 Aspergillus AF293 protein(XM_748400) 1096-1114 BP (SEQ ID NO: 851) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 125-1 Unmodified siRNA + 87% 0% 5-AGCGAUCCCGAACAAGUAUTT (SEQ ID NO: 913) TTUCGCUAGGGCUUGUUCAUA-5 (SEQ ID NO: 914) 125-2 Random modification (2′-O-methyl) ++ 34% 25%  5-AGCGAUCCCGAACAAGUAUTT (SEQ ID NO: 915) TTUCGCUAGGGCUUGUUCAUA-5 (SEQ ID NO: 916) 125-3A Specific modification (2′-O-methyl) ++ 84% 4% 5-AGCGAUCCCGAACAAG UAUTT (SEQ ID NO: 917) TTUCGCUAGGGCUUGUUCAU A-5 (SEQ ID NO: 918) 125-3B Specific modification (2′-O-methyl) ++ 85% 0% 5-AGCGAUCCCGAACAAGUAUTT (SEQ ID NO: 913) TTUCGCUAGGGCUUGUUCAU A-5 (SEQ ID NO: 919)

TABLE 126 Aspergillus AF293 protein(XM_748400) 1227-1245 BP (SEQ ID NO: 851) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 126-1 Unmodified siRNA + 77% 0% 5-CGAAAGUGUAUCCGAAGACTT (SEQ ID NO: 920) TTGCUUUCACAUAGGCUUCUG-5 (SEQ ID NO: 921) 126-2 Random modification (2′-deoxy-2′-fluoro) ++ 41% 22%  5-CGAAAGUGUAUCCGAAGACTT (SEQ ID NO: 922) TTGCUUUCACAUAGGCUUCUG-5 (SEQ ID NO: 923) 126-3A Specific modification (2′-deoxy-2′-fluoro) ++ 75% 3% 5-CGAAAGUG UAUCCGAAGACTT (SEQ ID NO: 924) TTGCUUUCAC AU AGGCUUCUG-5 (SEQ ID NO: 925) 126-3B Specific modification (2′-deoxy-2′-fluoro) ++ 69% 0% 5-CGAAAGUGUAUCCGAAGACTT (SEQ ID NO: 920) TTGCUUUCACAU AGGCUUCUG-5 (SEQ ID NO: 926)

TABLE 127 Aspergillus AF293 protein(XM_748400) 1238-1256 BP (SEQ ID NO: 851) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 127-1 Unmodified siRNA + 48% 0% 5-CCGAAGACGAAGCUAUGAATT (SEQ ID NO: 927) TTGGCUUCUGCUUCGAUACUU-5 (SEQ ID NO: 928) 127-2 Random modification (2′-deoxy-2′-fluoro) ++ 23% 19%  5-CCGAAGACGAAGCUAUGAATT (SEQ ID NO: 929) TTGGCUUCUGCUUCGAUACUU-5 (SEQ ID NO: 930) 127-3A Specific modification (2′-deoxy-2′-fluoro) ++ 46% 2% 5-CCGAAGACGAAGC UA UGAATT (SEQ ID NO: 931) TTGGCUUCUGCUUCGAU ACUU-5 (SEQ ID NO: 932) 127-3B Specific modification (2′-deoxy-2′-fluoro) ++ 47% 0% 5-CCGAAGACGAAGCUAUGAATT (SEQ ID NO: 927) TTGGCUUCUGCUUCGAU ACUU-5 (SEQ ID NO: 933)

TABLE 128 Human BIC(NR_001458.3) 170-188 BP (SEQ ID NO: 40) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 128-1 Unmodified siRNA + 83% 0% 5-UCUCCCACCCAAUGGAGAU (SEQ ID NO: 934) TTAGAGGGUGGGUUACCUCUA-5 (SEQ ID NO: 935) 128-2 Random modification (2′-O-methyl) ++ 49% 24%  5-UCUCCCACCCAAUGGAGAU (SEQ ID NO: 936) TTAGAGGGUGGGUUACCUCUA-5 (SEQ ID NO: 937) 128-3A Specific modification (2′-O-methyl) ++ 78% 9% 5-UCUCC CACC CA AUGGAGAU (SEQ ID NO: 938) TTAGAGGGU GGGUUACCUCUA-5 (SEQ ID NO: 939) 128-3B Specific modification (2′-O-methyl) ++ 81% 4% 5-UCUCCCACCCAAUGGAGAU (SEQ ID NO: 940) TTAGAGGGUGGGUUACCUCUA-5 (SEQ ID NO: 935)

TABLE 129 206-224 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 129-1 Unmodified siRNA + 69% 0% 5-AAACCAGGAAGGGGAAAUCTT (SEQ ID NO: 941) TTUUUGGUCCUUCCCCUUUAG-5 (SEQ ID NO: 942) 129-2 Random modification (2′-deoxy-2′-fluoro) ++ 42% 41%  5-AAACCAGGAAGGGGAAAUCTT (SEQ ID NO: 943) TTUUUGGUCCUUCCCCUUUAG-5 (SEQ ID NO: 944) 129-3A Specific modification (2′-deoxy-2′-fluoro) ++ 61% 9% 5-AAAC CA GGAAGGGGAAAUCTT (SEQ ID NO: 945) TTUUUG GU CCUUCCCCUUUAG-5 (SEQ ID NO: 946) 129-3B Specific modification (2′-deoxy-2′-fluoro) ++ 64% 3% 5-AAAC CA GGAAGGGGAAAUCTT (SEQ ID NO: 947) TTUUUGGUCCUUCCCCUUUAG-5 (SEQ ID NO: 942)

TABLE 130 213-231 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 130-1 Unmodified siRNA + 66% 0% 5-GAAGGGGAAAUCUGUGGUUTT (SEQ ID NO: 948) TTCUUCCCCUUUAGACACCAA-5 (SEQ ID NO: 949) 130-2 Random modification (2′-O-methyl) +++ 41% 24%  5-GAAGGGGAAAUCUGUGGUUTT (SEQ ID NO: 950) TTCUUCCCCUUUAGACACCAA-5 (SEQ ID NO: 949) 130-3A Specific modification (2′-O-methyl) +++ 61% 6% 5-GAAGGGGAAAUC UGUG GUUTT (SEQ ID NO: 951) TTCUUCCCCUUUAG ACAC CAA-5 (SEQ ID NO: 952) 130-3B Specific modification (2′-O-methyl) +++ 65% 2% 5-GAAGGGGAAAUC UGUGGUUTT (SEQ ID NO: 953) TTCUUCCCCUUUAGACAC CAA-5 (SEQ ID NO: 954)

TABLE 131 398-416 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 131-1 Unmodified siRNA + 86% 0% 5-GGGAGGAUGACAAAGAAGCTT (SEQ ID NO: 955) TTCCCUCCUACUGUUUCUUCG-5 (SEQ ID NO: 956) 131-2 Random modification (2′-deoxy-2′-fluoro) ++ 37% 19%  5-GGGAGGAUGACAAAGAAGCTT (SEQ ID NO: 955) TTCCCUCCUACUGUUUCUUCG-5 (SEQ ID NO: 957) 131-3A Specific modification (2′-deoxy-2′-fluoro) ++ 78% 9% 5-GGGAGGA UG A CAAAGAAGCTT (SEQ ID NO: 958) TTCCCUCCUAC UGU UUCUUCG-5 (SEQ ID NO: 959) 131-3B Specific modification (2′-deoxy-2′-fluoro) ++ 84% 2% 5-GGGAGGA UGA CAAAGAAGCTT (SEQ ID NO: 960) TTCCCUCCUACUGU UUCUUCG-5 (SEQ ID NO: 961)

TABLE 132 170-188 BP Human BIC(NR_001458.3) (SEQ ID NO: 40) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 132-1 Unmodified siRNA + 90% 0% 5-GAAACUGGUACUUUCCCCCTT (SEQ ID NO: 962) TTCUUUGACCAUGAAAGGGGG-5 (SEQ ID NO: 963) 132-2 Random modification (2′-O-methyl) ++ 57% 24%  5-GAAACUGGUACUUUCCCCCTT (SEQ ID NO: 964) TTCUUUGACCAUGAAAGGGGG-5 (SEQ ID NO: 963) 132-3A Specific modification (2′-O-methyl) ++ 85% 7% 5-GAAAC UG G UACUUUCCCCCTT (SEQ ID NO: 965) TTCUUUG AC CAU GAAAGGGGG-5 (SEQ ID NO: 966) 132-3B Specific modification (2′-O-methyl) ++ 88% 3% 5-GAAAC UG G UACUUUCCCCCTT (SEQ ID NO: 967) TTCUUUGACCAU GAAAGGGGG-5 (SEQ ID NO: 968)

TABLE 133 13-31 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 133-1 Unmodified siRNA + 72% 0% 5-AUCGCUGCUCCUCCUCCUCTT (SEQ ID NO: 960) TTUAGCGACGAGGAGGAGGAG-5 (SEQ ID NO: 970) 133-2 Random modification (2′-deoxy-2′-fluoro) ++ 39% 24%  5-AUCGCUGCUCCUCCUCCUCTT (SEQ ID NO: 971) TTUAGCGACGAGGAGGAGGAG-5 (SEQ ID NO: 1352) 133-3A Specific modification (2′-deoxy-2′-fluoro) ++ 69% 6% 5-AUCGC UGCUCCUCCUCCUCTT (SEQ ID NO: 972) TTUAGCGAC GAGGAGGAGGAG-5 (SEQ ID NO: 973) 133-3B Specific modification (2′-deoxy-2′-fluoro) ++ 71% 1% 5-AUCGC UGCUCCUCCUCCUCTT (SEQ ID NO: 974) TTUAGCGAC GAGGAGGAGGAG-5 (SEQ ID NO: 975)

TABLE 134 239-257 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 134-1 Unmodified siRNA + 39% 0% 5-AGCUCUUUGUCACCUCUCUTT (SEQ ID NO: 976) TTUCGAGAAACAGUGGAGAGA-5 (SEQ ID NO: 977) 134-2 Random modification (2′-O-methyl) ++ 19% 24%  5-AGCUCUUUGUCACCUCUCUTT (SEQ ID NO: 978) TTUCGAGAAACAGUGGAGAGA-5 (SEQ ID NO: 979) 134-3A Specific modification (2′-O-methyl) ++ 34% 9% 5-AGCUCUU UGU CACCUCUCUTT (SEQ ID NO: 980) TTUCGAGAAAC AGU GGAGAGA-5 (SEQ ID NO: 981) 134-3B Specific modification (2′-O-methyl) ++ 37% 3% 5-AGCUCUUUGUCA CCUCUCUTT (SEQ ID NO: 982) TTUCGAGAA AC AGUGGAGAGA-5 (SEQ ID NO: 983)

TABLE 135 294-312 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 135-1 Unmodified siRNA + 58% 0% 5-AAUAAGCAGCUCGCGCUCCTT (SEQ ID NO: 984) TTUUAUUCGUCGAGCGCGAGG-5 (SEQ ID NO: 985) 135-2 Random modification (2′-O-methyl) ++ 32% 24%  5-AAUAAGCAGCUCGCGCUCCTT (SEQ ID NO: 986) TTUUAUUCGUCGAGCGCGAGG-5 (SEQ ID NO: 987) 135-3A Specific modification (2′-O-methyl) ++ 51% 9% 5-AA UAAG CAGCUCGCGCUCCTT (SEQ ID NO: 988) TTUUAU UCGU CGAGCGCGAGG-5 (SEQ ID NO: 989) 135-3B Specific modification (2′-O-methyl) ++ 54% 2% 5-AA UAAG CAGCUCGCGCUCCTT (SEQ ID NO: 990) TTUUAU UCGUCGAGCGCGAGG-5 (SEQ ID NO: 991)

TABLE 136 1383-1401 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 136-1 Unmodified siRNA + 97% 0% 5-CUAGAGGAUCUUGAAGACCTT (SEQ ID NO: 992) TTGAUCUCCUAGAACUUCUGG-5 (SEQ ID NO: 993) 136-2 Random modification (2′-deoxy-2′-fluoro) ++ 38% 29%  5-CUAGAGGAUCUUGAAGACCTT (SEQ ID NO: 994) TTGAUCUCCUAGAACUUCUGG-5 (SEQ ID NO: 995) 136-3A Specific modification (2′-deoxy-2′-fluoro) ++ 91% 5% 5-C UAGAGGAUCU UGAAGACCTT (SEQ ID NO: 996) TTGAU CUCCUAGAAC UUCUGG-5 (SEQ ID NO: 997) 136-3B Specific modification (2′-deoxy-2′-fluoro) ++ 95% 1% 5-CUAGAGGAUCUUGAAGACCTT (SEQ ID NO: 992) TTGAU CUCCUAGAAC UUCUGG-5 (SEQ ID NO: 998)

TABLE 137 2151-2169 BP Human KAZRIN(NM_201628) (SEQ ID NO: 1) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 137-1 Unmodified siRNA + 32% 0% 5-AUCGACCUGAAGGAGUACGTT (SEQ ID NO: 999) TTUAGCUGGACUUCCUCAUGC-5 (SEQ ID NO: 1000) 137-2 Random modification (2′-O-methyl) ++ 19% 24%  5-AUCGACCUGAAGGAGUACGTT (SEQ ID NO: 1001) TTUAGCUGGACUUCCUCAUGC-5 (SEQ ID NO: 1002) 137-3A Specific modification (2′-O-methyl) ++ 29% 6% 5-AUCGACC UGAAGGAG UACGTT (SEQ ID NO: 1003) TTUAGCUGGAC UUCCUCAU GC-5 (SEQ ID NO: 1004) 137-3B Specific modification (2′-O-methyl) ++ 30% 1% 5-AUCGACC UGAAGGAG UACGTT (SEQ ID NO: 1005) TTUAGCUGGACUUCCUCAU GC-5 (SEQ ID NO: 1006)

TABLE 138 80-98 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 138-1 Unmodified siRNA + 75% 0% 5-CCCUCCCCUGUCCCCGCUUTT (SEQ ID NO: 1007) TTGGGAGGGGACAGGGGCGAA-5 (SEQ ID NO: 1008) 138-2 Random modification (2′-deoxy-2′-fluoro) ++ 41% 34%  5-CCCUCCCCUGUCCCCGCUUTT (SEQ ID NO: 1009) TTGGGAGGGGACAGGGGCGAA-5 (SEQ ID NO: 1010) 138-3A Specific modification (2′-deoxy-2′-fluoro) ++ 72% 3% 5-CCCUCCCC UGUCCCCGCUUTT (SEQ ID NO: 1011) TTGGGAGGGGAC AGGGGCGAA-5 (SEQ ID NO: 1012) 138-3B Specific modification (2′-deoxy-2′-fluoro) ++ 73% 1% 5-CCCUCCCC UGUCCCCGCUUTT (SEQ ID NO: 1013) TTGGGAGGGGACAGGGGCGAA-5 (SEQ ID NO: 1014)

TABLE 139 431-449 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 139-1 Unmodified siRNA + 94% 0% 5-UUUGAUCAGCGGAGACUCGTT (SEQ ID NO: 1014) TTAAACUAGUCGCCUCUGAGC-5 (SEQ ID NO: 1015) 139-2 Random modification (2′-O-methyl) ++ 49% 31%  5-UUUGAUCAGCGGAGACUCGTT (SEQ ID NO: 1016) TTAAACUAGUCGCCUCUGAGC-5 (SEQ ID NO: 1017) 139-3A Specific modification (2′-O-methyl) ++ 89% 3% 5-UU UGAU CAGCGGAGACUCGTT (SEQ ID NO: 1018) TTAAAC UAGU CGCCUCUGAGC-5 (SEQ ID NO: 1019) 139-3B Specific modification (2′-O-methyl) ++ 82% 0.5%   5-UUUG AU CAGCGGAGACUCGTT (SEQ ID NO: 1020) TTAAACUAGUCGCCUCUGAGC-5 (SEQ ID NO: 1015)

TABLE 140 591-609 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 140-1 Unmodified siRNA + 93% 0% 5-AGUUAACCCGGGACUUGGATT (SEQ ID NO: 1021) TTUCAAUUGGGCCCUGAACCU-5 (SEQ ID NO: 1022) 140-2 Random modification (2′-O-methyl) ++ 45% 34%  5-AGUUAACCCGGGACUUGGATT (SEQ ID NO: 1023) TTUCAAUUGGGCCCUGAACCU-5 (SEQ ID NO: 1024) 140-3A Specific modification (2′-O-methyl) ++ 90% 3% 5-AGU UAACCCGGGACU UGGATT (SEQ ID NO: 1025) TTUCAAU UGGGCCCUGAAC CU-5 (SEQ ID NO: 1026) 140-3B Specific modification (2′-O-methyl) ++ 91% 1% 5-AGU UAACCCGGGACUUGGATT (SEQ ID NO: 1027) TTUCAAUUGGGCCCUGAAC CU-5 (SEQ ID NO: 1028)

TABLE 141 669-687 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 141-1 Unmodified siRNA + 77% 0% 5-AUCACAAACCCCUAGAGGGTT (SEQ ID NO: 1029) TTUAGUGUUUGGGGAUCUCCC-5 (SEQ ID NO: 1030) 141-2 Random modification (2′-O-methyl) ++ 35% 31%  5-AUCACAAACCCCUAGAGGGTT (SEQ ID NO: 1031) TTUAGUGUUUGGGGAUCUCCC-5 (SEQ ID NO: 1032) 141-3A Specific modification (2′-O-methyl) ++ 75% 4% 5-AU CACAAACCCC UAGAGGGTT (SEQ ID NO: 1033) TTUAGUGU UUGGGGAU CUCCC-5 (SEQ ID NO: 1034) 141-3B Specific modification (2′-O-methyl) ++ 75% 1% 5-AU CACAAACCCCUAGAGGGTT (SEQ ID NO: 1035) TTUAGUGUUUGGGGAU CUCCC-5 (SEQ ID NO: 1036)

TABLE 142 674-692 BP Human CDKN1B(NM_004064) (SEQ ID NO: 217) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 142-1 Unmodified siRNA + 84% 0% 5-AAACCCCUAGAGGGCAAGUTT (SEQ ID NO: 1037) TTUUUGGGGAUCUCCCGUUCA-5 (SEQ ID NO: 1038) 142-2 Random modification (2′-deoxy-2′-fluoro) ++ 37% 29%  5-AAACCCCUAGAGGGCAAGUTT (SEQ ID NO: 1029) TTUUUGGGGAUCUCCCGUUCA-5 (SEQ ID NO: 1039) 142-3A Specific modification (2′-deoxy-2′-fluoro) ++ 82% 5% 5-AAACCCC UAGAGGG CAAGUTT (SEQ ID NO: 1040) TTUUUGGGGAU CUCCCGU UCA-5 (SEQ ID NO: 1041) 142-3B Specific modification (2′-deoxy-2′-fluoro) ++ 83% 1% 5-AAACCCC UAGAGGG CAAGUTT (SEQ ID NO: 1042) TTUUUGGGGAUCUCCCGUUCA-5 (SEQ ID NO: 1038)

TABLE 143 Chinpanzee SOD2(NM_001009022) 45-63 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 143-1 Unmodified siRNA + 70%  0% 5-GGAACCUCACAUCAACGCGCATT (SEQ ID NO: 1043) TTCCUUGGAGUGUAGUUGCGCGU-5 (SEQ ID NO: 1044) 143-2 Random modification (2′-deoxy-2′-fluoro) ++ 21% 43% 5-GGAACCUCACAUCAACGCGCATT (SEQ ID NO: 1045) TTCCUUGGAGUGUAGUUGCGCGU-5 (SEQ ID NO: 1046) 143-3A Specific modification (2′-deoxy-2′-fluoro) ++ 52% 11% 5-GGAACCU CACAU CAACGCG CATT (SEQ ID NO: 1047) TTCCUUGGAGUGU AGU UGCGCGU -5 (SEQ ID NO: 1048) 143-3B Specific modification (2′-deoxy-2′-fluoro) ++ 65%  4% 5-GGAACCU CACAUCAACGCGCATT (SEQ ID NO: 1049) TTCCUUGGAGUGU AGU UGCGC GU-5 (SEQ ID NO: 1050)

TABLE 144 Chimpanzee SOD2(NM_001009022) 116-134 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 144-1 Unmodified siRNA + 87% 0% 5-UGAACGUCACCGAGGAGAATT (SEQ ID NO: 1051) TTACUUGCAGUGGCUCCUCUU-5 (SEQ ID NO: 1052) 144-2 Random modification (2′-O-methyl) ++ 65% 24%  5-UGAACGUCACCGAGGAGAATT (SEQ ID NO: 1053) TTACUUGCAGUGGCUCCUCUU-5 (SEQ ID NO: 1054) 144-3A Specific modification (2′-O-methyl) ++ 82% 5% 5- UGAACGU CACCGAGGAGAATT (SEQ ID NO: 1055) TTAC UUGCAGU GGCUCCUCUU-5 (SEQ ID NO: 1056) 144-3B Specific modification (2′-O-methyl) ++ 85% 1% 5-UGAACGU CACCGAGGAGAATT (SEQ ID NO: 1057) TTAC UUGCAGUGGCUCCUCUU-5 (SEQ ID NO: 1058)

TABLE 145 Chimpanzee SOD2(NM_001009022) 266-284 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 145-1 Unmodified siRNA + 97% 0% 5-AACCCAAAGGGGAGUUGCUTT (SEQ ID NO: 1059) TTUUGGGUUUCCCCUCAACGA-5 (SEQ ID NO: 1060) 145-2 Random modification (2′-O-methyl) ++ 37% 49%  5-AACCCAAAGGGGAGUUGCUTT (SEQ ID NO: 1061) TTUUGGGUUUCCCCUCAACGA-5 (SEQ ID NO: 1062) 145-3A Specific modification (2′-O-methyl) ++ 92% 6% 5-AACC CAAAGGGGAGU UGCUTT (SEQ ID NO: 1063) TTUUGGGU UUCCCCUCAAC GA-5 (SEQ ID NO: 1064) 145-3B Specific modification (2′-O-methyl) ++ 83% 1% 5-AACCCAAAGGGGAGU UGCUTT (SEQ ID NO: 1065) TTUUGGGU UUCCCCUCAACGA-5 (SEQ ID NO: 1066)

TABLE 146 Chimpanzee SOD2(NM_001009022) 274-292 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 146-1 Unmodified siRNA + 77% 0% 5-AAAGGGGAGUUGCUGGAAGTT (SEQ ID NO: 1067) TTUUUCCCCUCAACGACCUUC-5 (SEQ ID NO: 1068) 146-2 Random modification (2′-O-methyl) ++ 47% 31%  5-AAAGGGGAGUUGCUGGAAGTT (SEQ ID NO: 1069) TTUUUCCCCUCAACGACCUUC-5 (SEQ ID NO: 1070) 146-3A Specific modification (2′-O-methyl) ++ 74% 4% 5-AAAGGGGAGU UGC UGGAAGTT (SEQ ID NO: 1071) TTUUUCCCCUCAAC GAC CUUC-5 (SEQ ID NO: 1072) 146-3B Specific modification (2′-O-methyl) ++ 76% 1% 5-AAAGGGGAGU UGCUGGAAGTT (SEQ ID NO: 1073) TTUUUCCCCUCAACGAC CUUC-5 (SEQ ID NO: 1074)

TABLE 147 Chimpanzee SOD2(NM_001009022) 295-313 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 147-1 Unmodified siRNA + 86% 0% 5-AAACGUGACUUUGGUUCCUTT (SEQ ID NO: 1075) TTUUUGCACUGAAACCAAGGA-5 (SEQ ID NO: 1076) 147-2 Random modification (2′-O-methyl) ++ 37% 29%  5-AAACGUGACUUUGGUUCCUTT (SEQ ID NO: 1077) TTUUUGCACUGAAACCAAGGA-5 (SEQ ID NO: 1078) 147-3A Specific modification (2′-O-methyl) ++ 82% 5% 5-AAACG UGACUU UGGUUCCUTT (SEQ ID NO: 1079) TTUUUGCAC UGAAAC CAAGGA-5 (SEQ ID NO: 1080) 147-3B Specific modification (2′-O-methyl) ++ 83% 1% 5-AAACGUGACUU UGGUUCCUTT (SEQ ID NO: 1081) TTUUUGCAC UGAAACCAAGGA-5 (SEQ ID NO: 1082)

TABLE 148 Chimpanzee SOD2(NM_001009022) 108-126 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 148-1 Unmodified siRNA + 72%  0% 5-GAAUAACCUGAACGUCACCTT (SEQ ID NO: 1083) TTCUUAUUGGACUUGCAGUGG-5 (SEQ ID NO: 1084) 148-2 Random modification (2′-O-methyl) ++ 21% 19% 5-GAAUAACCUGAACGUCACCTT (SEQ ID NO: 1085) TTCUUAUUGGACUUGCAGUGG-5 (SEQ ID NO: 1086) 148-3A Specific modification (2′-O-methyl) ++ 69% 10% 5-GAA UAACC UGAACGU CACCTT (SEQ ID NO: 1087) TTCUUAU UGGAC UUGCAGU GG-5 (SEQ ID NO: 1088) 148-3B Specific modification (2′-O-methyl) ++ 71%  3% 5-GAA UAACCUGAACGU CACCTT (SEQ ID NO: 1089) TTCUUAUUGGAC UUGCAGUGG-5 (SEQ ID NO: 1090)

TABLE 149 Chimpanzee SOD2(NM_001009022) 119-137 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 149-1 Unmodified siRNA + 81% 0% 5-ACGUCACCGAGGAGAAGUATT (SEQ ID NO: 1091) TTUGCAGUGGCUCCUCUUCAU-5 (SEQ ID NO: 1092) 149-2 Random modification (2′-O-methyl) ++ 31% 26%  5-ACGUCACCGAGGAGAAGUATT (SEQ ID NO: 1093) TTUGCAGUGGCUCCUCUUCAU-5 (SEQ ID NO: 1094) 149-3A Specific modification (2′-O-methyl) ++ 75% 6% 5-ACGU CACCGAGGAGAAG UA TT (SEQ ID NO: 1095) TTUGCAGU GGCUCCUCUUC AU -5 (SEQ ID NO: 1096) 149-3B Specific modification (2′-O-methyl) ++ 80% 1% 5-ACGU CACCGAGGAGAAGUATT (SEQ ID NO: 1097) TTUGCAGU GGCUCCUCUUCAU -5 (SEQ ID NO: 1098)

TABLE 150 Chimpanzee SOD2(NM_001009022) 131-149 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 150-1 Unmodified siRNA + 62% 0% 5-AGAAGUACCAGGAGGCGUUTT (SEQ ID NO: 1099) TTUCUUCAUGGUCCUCCGCAA-5 (SEQ ID NO: 1100) 150-2 Random modification (2′-deoxy-2′-fluoro) ++ 39% 35%  5-AGAAGUACCAGGAGGCGUUTT (SEQ ID NO: 1101) TTUCUUCAUGGUCCUCCGCAA-5 (SEQ ID NO: 1102) 150-3A Specific modification (2′-deoxy-2′-fluoro) ++ 57% 3% 5-AGAAG UAC CAGGAGGCGUUTT (SEQ ID NO: 1103) TTUCUUCAU GGU CCUCCGCAA-5 (SEQ ID NO: 1104) 150-3B Specific modification (2′-deoxy-2′-fluoro) ++ 60% 1% 5-AGAAG UACCAGGAGGCGUUTT (SEQ ID NO: 1105) TTUCUUCAUGGU CCUCCGCAA-5 (SEQ ID NO: 1106)

TABLE 151 Chimpanzee SOD2(NM_001009022) 240-258 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 151-1 Unmodified siRNA + 71% 0% 5-AAACCUCAGCCCUAACGGUTT (SEQ ID NO: 1107) TTUUUGGAGUCGGGAUUGCCA-5 (SEQ ID NO: 1108) 151-2 Random modification (2′-O-methyl) ++ 28% 27%  5-AAACCUCAGCCCUAACGGUTT (SEQ ID NO: 1109) TTUUUGGAGUCGGGAUUGCCA-5 (SEQ ID NO: 1110) 151-3A Specific modification (2′-O-methyl) ++ 70% 3% 5-AAACCU CAGCCC UAACGGUTT (SEQ ID NO: 1111) TTUUUGGAGU CGGGAU UGCCA-5 (SEQ ID NO: 1112) 151-3B Specific modification (2′-O-methyl) ++ 70% 1% 5-AAACCUCA GCCCUAACGGUTT (SEQ ID NO: 1113) TTUUUGGAGUCGGGAU UGCCA-5 (SEQ ID NO: 1114)

TABLE 152 chimpanzee SOD2(NM_001009022) 323-341 BP (SEQ ID NO: 321) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 152-1 Unmodified siRNA + 87% 0% 5-UUAAGGAGAAGCUGACGGCTT (SEQ ID NO: 1115) TTAAUUCCUCUUCGACUGCCG-5 (SEQ ID NO: 1116) 152-2 Random modification (2′-O-methyl) ++ 45% 24%  5-UUAAGGAGAAGCUGACGGCTT (SEQ ID NO: 1117) TTAAUUCCUCUUCGACUGCCG-5 (SEQ ID NO: 1118) 152-3A Specific modification (2′-O-methyl) ++ 82% 4% 5-U UAAGGAGAAGC UG ACGGCTT (SEQ ID NO: 1119) TTAAU UCCUCUUCGAC UGCCG-5 (SEQ ID NO: 1120) 152-3B Specific modification (2′-O-methyl) ++ 83% 1% 5-U UAAGGAGAAGCUGACGGCTT (SEQ ID NO: 1121) TTAAU UCCUCUUCGAC UGCCG-5 (SEQ ID NO: 1122)

TABLE 153 rhesus monkey RECEPTOR (XM_001111972) 3-21 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 153-1 Unmodified siRNA + 75% 0% 5-AACUUCUGGGAGCCUCCAATT (SEQ ID NO: 1123) TTUUGAAGACCCUCGGAGGUU-5 (SEQ ID NO: 1124) 153-2 Random modification (2′-O-methyl) ++ 42% 27%  5-AACUUCUGGGAGCCUCCAATT (SEQ ID NO: 1125) TTUUGAAGACCCUCGGAGGUU-5 (SEQ ID NO: 1126) 153-3A Specific modification (2′-O-methyl) ++ 69% 4% 5-AACUUC UGGGAGCCUC CAATT (SEQ ID NO: 1127) TTUUGAAGAC CCUCGGAGGU U-5 (SEQ ID NO: 1128) 153-3B Specific modification (2′-O-methyl) ++ 73% 1% 5-AACUUCUGGGAGCCUC CAATT (SEQ ID NO: 1129) TTUUGAAGAC CCUCGGAGGUU-5 (SEQ ID NO: 1130)

TABLE 154 Rhesus monkey RECEPTOR(XM_001111972) 80-98 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 154-1 Unmodified siRNA + 87% 0% 5-CCAGCGAGCCCAAAAGAAATT (SEQ ID NO: 1131) TTGGUCGCUCGGGUUUUCUUU-5 (SEQ ID NO: 1132) 154-2 Random modification (2′-deoxy-2′-fluoro) ++ 35% 24%  5-CCAGCGAGCCCAAAAGAAATT (SEQ ID NO: 1133) TTGGUCGCUCGGGUUUUCUUU-5 (SEQ ID NO: 1134) 154-3A Specific modification (2′-deoxy-2′-fluoro) ++ 82% 5% 5-C CAGCGAGCC CAAAAGAAATT (SEQ ID NO: 1135) TTGGU CGCUCGGGU UUUCUUU-5 (SEQ ID NO: 1136) 154-3B Specific modification (2′-deoxy-2′-fluoro) ++ 85% 1% 5-C CAGCGAGCC CAAAAGAAATT (SEQ ID NO: 1137) TTGGUCGCUCGGGUUUUCUUU-5 (SEQ ID NO: 1132)

TABLE 155 Rhesus monkey RECEPTOR (XM_001111972) 216-234 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 155-1 Unmodified siRNA + 86% 0% 5-CUCAAAUCAAGGCCGGAGUTT (SEQ ID NO: 1138) TTGAGUUUAGUUCCGGCCUCA-5 (SEQ ID NO: 1139) 155-2 Random modification (2′-O-methyl) ++ 36% 34%  5-CUCAAAUCAAGGCCGGAGUTT (SEQ ID NO: 1140) TTGAGUUUAGUUCCGGCCUCA-5 (SEQ ID NO: 1141) 155-3A Specific modification (2′-O-methyl) ++ 82% 4% 5-CU CAAAU CAAGGCCGGAGUTT (SEQ ID NO: 1142) TTGAGU UUAGU UCCGGCCUCA-5 (SEQ ID NO: 1143) 155-3B Specific modification (2′-O-methyl) ++ 85% 1% 5-CUCAAAUCAAGGCCGGAGUTT (SEQ ID NO: 1138) TTGAGU UUAGU UCCGGCCUCA-5 (SEQ ID NO: 1144)

TABLE 156 Rhesus monkey RECEPTOR (XM_001111972) 13-31 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 156-1 Unmodified siRNA + 71% 0% 5-AGCCUCCAAACUCCUAGCUTT (SEQ ID NO: 1145) TTUCGGAGGUUUGAGGAUCGA-5 (SEQ ID NO: 1146) 156-2 Random modification (2′-O-methyl) ++ 47% 19%  5-AGCCUCCAAACUCCUAGCUTT (SEQ ID NO: 1147) TTUCGGAGGUUUGAGGAUCGA-5 (SEQ ID NO: 1148) 156-3A Specific modification (2′-O-methyl) ++ 65% 3% 5-AGCCUC CAAACUCC UAGCUTT (SEQ ID NO: 1149) TTUCGGAGGU UUGAGGAU CGA-5 (SEQ ID NO: 1150) 156-3B Specific modification (2′-O-methyl) ++ 70% 1% 5-AGCCUCCAAACUCCUAGCUTT (SEQ ID NO: 1145) TTUCGGAGGU UUGAGGAU CGA-5 (SEQ ID NO: 1151)

TABLE 157 Rhesus monkey RECEPTOR (XM_001111972) 162-180 BP (SEQ ID NO: 383) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 157-1 Unmodified siRNA + 73% 0% 5-AUACUUGGCGGGCUCUUUCTT (SEQ ID NO: 1152) TTUAUGAACCGCCCGAGAAAG-5 (SEQ ID NO: 1153) 157-2 Random modification (2′-O-methyl) ++ 25% 31%  5-AUACUUGGCGGGCUCUUUCTT (SEQ ID NO: 1154) TTUAUGAACCGCCCGAGAAAG-5 (SEQ ID NO: 1155) 157-3A Specific modification (2′-O-methyl) ++ 70% 4% 5-A UACU UG GCGGGCUCUUUCTT (SEQ ID NO: 1156) TTUAU GAAC CGCCCGAGAAAG-5 (SEQ ID NO: 1157) 157-3B Specific modification (2′-O-methyl) ++ 72% 1% 5-AUA CUUGGCGGGCUCUUUCTT (SEQ ID NO: 1158) TTUAUGAAC CGCCCGAGAAAG-5 (SEQ ID NO: 1159)

TABLE 158 Dog B cell lymphoma(NM_001003016) 508-526 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 158-1 Unmodified siRNA + 84% 0% 5-UUGGGGAAGCGGCCGGCGGTT (SEQ ID NO: 1160) TTAACCCCUUCGCCGGCCGCC-5 (SEQ ID NO: 1161) 158-2 Random modification (2′-O-methyl) ++ 36% 27%  5-UUGGGGAAGCGGCCGGCGGTT (SEQ ID NO: 1162) TTAACCCCUUCGCCGGCCGCC-5 (SEQ ID NO: 1163) 158-3A Specific modification (2′-O-methyl) ++ 78% 5% 5-U UG GGGAAGCGGCCGGCGGTT (SEQ ID NO: 1164) TTAAC CCCUUCGCCGGCCGCC-5 (SEQ ID NO: 1165) 158-3B Specific modification (2′-O-methyl) ++ 82% 1% 5-U UGGGGAAGCGGCCGGCGGTT (SEQ ID NO: 1166) TTAAC CCCUUCGCCGGCCGCC-5 (SEQ ID NO: 1167)

TABLE 159 Dog B cell lymphoma(NM_001003016) 794-812 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 159-1 Unmodified siRNA + 96% 0% 5-AAGGCAUGCUUCGGAAACUTT (SEQ ID NO: 1168) TTUUCCGUACGAAGCCUUUGA-5 (SEQ ID NO: 1169) 159-2 Random modification (2′-O-methyl) ++ 60% 35%  5-AAGGCAUGCUUCGGAAACUTT (SEQ ID NO: 1170) TTUUCCGUACGAAGCCUUUGA-5 (SEQ ID NO: 1171) 159-3A Specific modification (2′-O-methyl) ++ 87% 6% 5-AAGG CAUG CUUCGGAAACUTT (SEQ ID NO: 1172) TTUUCCGUAC GAAGCCUUUGA-5 (SEQ ID NO: 1173) 159-3B Specific modification (2′-O-methyl) ++ 95% 1% 5-AAGG CAUGCUUCGGAAACUTT (SEQ ID NO: 1174) TTUUCCGUAC GAAGCCUUUGA-5 (SEQ ID NO: 1175)

TABLE 160 Dog B cell lymphoma(NM_001003016) 801-819 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 160-1 Unmodified siRNA + 91% 0% 5-GCUUCGGAAACUGGACAUCTT (SEQ ID NO: 1176) TTCGAAGCCUUUGACCUGUAG-5 (SEQ ID NO: 1177) 160-2 Random modification (2′-deoxy-2′-fluoro) ++ 29% 37%  5-GCUUCGGAAACUGGACAUCTT (SEQ ID NO: 1178) TTCGAAGCCUUUGACCUGUAG-5 (SEQ ID NO: 1179) 160-3A Specific modification (2′-deoxy-2′-fluoro) ++ 87% 5% 5-GCUUCGGAAAC UG GA CAUCTT (SEQ ID NO: 1180) TTCGAAGCCUUUG AC CUGU AG-5 (SEQ ID NO: 1181) 160-3B Specific modification (2′-deoxy-2′-fluoro) ++ 90% 1% 5-GCUUCGGAAACUGGA CAUCTT (SEQ ID NO: 1182) TTCGAAGCCUUUGAC CUGU AG-5 (SEQ ID NO: 1183)

TABLE 161 Dog B cell lymphoma(NM_001003016) 21-39 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 161-1 Unmodified siRNA + 73% 0% 5-AACUCUACUGUGGAGUCGGTT (SEQ ID NO: 1184) TTUUGAGAUGACACCUCAGCC-5 (SEQ ID NO: 1185) 161-2 Random modification (2′-deoxy-2′-fluoro) ++ 25% 31%  5-AACUCUACUGUGGAGUCGGTT (SEQ ID NO: 1186) TTUUGAGAUGACACCUCAGCC-5 (SEQ ID NO: 1187) 161-3A Specific modification (2′-deoxy-2′-fluoro) ++ 65% 8% 5-AACUC UAC UGUGGAGUCGGTT (SEQ ID NO: 1188) TTUUGAGAU GACAC CUCAGCC-5 (SEQ ID NO: 1189) 161-3B Specific modification (2′-deoxy-2′-fluoro) ++ 72% 2% 5-AACUCUAC UGUGGAGUCGGTT (SEQ ID NO: 1190) TTUUGAGAU GACAC CUCAGCC-5 (SEQ ID NO: 1191)

TABLE 162 Dog B cell lymphoma(NM_001003016) 124-142 BP (SEQ ID NO: 498) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 162-1 Unmodified siRNA + 87% 0% 5-AGAAACGCAGUAAUCCGGATT (SEQ ID NO: 1192) TTUCUUUGCGUCAUUAGGCCU-5 (SEQ ID NO: 1193) 162-2 Random modification (2′-O-methyl) ++ 36% 27%  5-AGAAACGCAGUAAUCCGGATT (SEQ ID NO: 1194) TTUCUUUGCGUCAUUAGGCCU-5 (SEQ ID NO: 1195) 162-3A Specific modification (2′-O-methyl) ++ 78% 5% 5-AGAAACG CAG UA AUCCGGATT (SEQ ID NO: 1196) TTUCUUUGCGU CAU UAGGCCU-5 (SEQ ID NO: 1197) 162-3B Specific modification (2′-O-methyl) ++ 82% 1% 5-AGAAACGCAG UAAUCCGGATT (SEQ ID NO: 1198) TTUCUUUGCGU CAUUAGGCCU-5 (SEQ ID NO: 1199)

TABLE 163 rat(NM_001014070.1) 447-465 BP (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 163-1 Unmodified siRNA + 55% 0% 5-GGAAGUCCACCUUCUCCGATT (SEQ ID NO: 1200) TTCCUUCAGGUGGAAGAGGCU-5 (SEQ ID NO: 1201) 163-2 Random modification (2′-O-methyl) ++ 27% 31%  5-GGAAGUCCACCUUCUCCGATT (SEQ ID NO: 1202) TTCCUUCAGGUGGAAGAGGCU-5 (SEQ ID NO: 1203) 163-3A Specific modification (2′-O-methyl) ++ 51% 5% 5-GGAAGUC CA CCUUCUCCGATT (SEQ ID NO: 1204) TTCCUUCAGGU GGAAGAGGCU-5 (SEQ ID NO: 1205) 163-3B Specific modification (2′-O-methyl) ++ 54% 1% 5-GGAAGUCCA CCUUCUCCGATT (SEQ ID NO: 1206) TTCCUUCAGGU GGAAGAGGCU-5 (SEQ ID NO: 1207)

TABLE 164 rat(NM_001014070.1) 460-478 BP (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 164-1 Unmodified siRNA + 73% 0% 5-CUCCGACAGAUGAAGGAAATT (SEQ ID NO: 1208) TTGAGGCUGUCUACUUCCUUU-5 (SEQ ID NO: 1209) 164-2 Random modification (2′-O-methyl) ++ 46% 21%  5-CUCCGACAGAUGAAGGAAATT (SEQ ID NO: 1210) TTGAGGCUGUCUACUUCCUUU-5 (SEQ ID NO: 1211) 164-3A Specific modification (2′-O-methyl) ++ 70% 6% 5-CUCCGA CA GA UGAAGGAAATT (SEQ ID NO: 1212) TTGAGGCU GU CUAC UUCCUUU-5 (SEQ ID NO: 1213) 164-3B Specific modification (2′-O-methyl) ++ 72% 1% 5-CUCCGACAGA UGAAGGAAATT (SEQ ID NO: 1214) TTGAGGCUGU CUACUUCCUUU-5 (SEQ ID NO: 1215)

TABLE 165 rat(NM_001014070.1) 487-505 BP (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 165-1 Unmodified siRNA + 83% 0% 5-AAGGACCUAGAGGAGUCACTT (SEQ ID NO: 1216) TTUUCCUGGAUCUCCUCAGUG-5 (SEQ ID NO: 1217) 165-2 Random modification (2′-O-methyl) ++ 36% 27%  5-AAGGACCUAGAGGAGUCACTT (SEQ ID NO: 1218) TTUUCCUGGAUCUCCUCAGUG-5 (SEQ ID NO: 1219) 165-3A Specific modification (2′-O-methyl) ++ 78% 5% 5-AAGGACC UAGAGGAGU CA CTT (SEQ ID NO: 1220) TTUUCCUGGAU CUCCUCAGU G-5 (SEQ ID NO: 1221) 165-3B Specific modification (2′-O-methyl) ++ 80% 1% 5-AAGGACC UAGAGGAGUCACTT (SEQ ID NO: 1222) TTUUCCUGGAUCUCCUCAGU G-5 (SEQ ID NO: 1223)

TABLE 166 614-632 BP rat(NM_001014070.1) (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 166-1 Unmodified siRNA + 90% 0% 5-CUGACCGGAAGCGCUUAAATT (SEQ ID NO: 1224) TTGACUGGCCUUCGCGAAUUU-5 (SEQ ID NO: 1225) 166-2 Random modification (2′-deoxy-2′-fluoro) ++ 59% 24%  5-CUGACCGGAAGCGCUUAAATT (SEQ ID NO: 1226) TTGACUGGCCUUCGCGAAUUU-5 (SEQ ID NO: 1227) 166-3A Specific modification (2′-deoxy-2′-fluoro) ++ 85% 4% 5-C UGACCGGAAGCGCU UAAATT (SEQ ID NO: 1228) TTGAC UGGCCUUCGCGAAU UU-5 (SEQ ID NO: 1229) 166-3B Specific modification (2′-deoxy-2′-fluoro) ++ 87% 1% 5-C UGACCGGAAGCGCUUAAATT (SEQ ID NO: 1230) TTGACUGGCCUUCGCGAAU UU-5 (SEQ ID NO: 1231)

TABLE 167 rat(NM_001014070.1) 1257-1275 BP (SEQ ID NO: 608) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 167-1 Unmodified siRNA + 76% 0% 5-GAAGAGCCUACACAACCCUTT (SEQ ID NO: 1232) TTCUUCUCGGAUGUGUUGGGA-5 (SEQ ID NO: 1233) 167-2 Random modification (2′-O-methyl) ++ 43% 31%  5-GAAGAGCCUACACAACCCUTT (SEQ ID NO: 1234) TTCUUCUCGGAUGUGUUGGGA-5 (SEQ ID NO: 1235) 167-3A Specific modification (2′-O-methyl) ++ 74% 10%  5-GAAGAGCC UACACAACCCUTT (SEQ ID NO: 1236) TTCUUCUCGGAUGUGU UGGGA-5 (SEQ ID NO: 1237) 167-3B Specific modification (2′-O-methyl) ++ 74% 3% 5-GAAGAGCCUACACAACCCUTT (SEQ ID NO: 1238) TTCUUCUCGGAUGUGU UGGGA-5 (SEQ ID NO: 1239)

TABLE 168 Rat BIRC5(NM_022274) 364-382 BP (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 168-1 Unmodified siRNA + 65%  0% 5-ACAGAAAGAGUUCGAGGAGTT (SEQ ID NO: 1240) TTUGUCUUUCUCAAGCUCCUC-5 (SEQ ID NO: 1241) 168-2 Random modification (2′-O-methyl) ++ 37% 28% 5-ACAGAAAGAGUUCGAGGAGTT (SEQ ID NO: 1242) TTUGUCUUUCUCAAGCUCCUC-5 (SEQ ID NO: 1243) 168-3A Specific modification (2′-O-methyl) ++ 61%  6% 5-A CA GAAAGAGUUCGAGGAGTT (SEQ ID NO: 1244) TTUGU CUUUCUCAAGCUCCUC-5 (SEQ ID NO: 1245) 168-3B Specific modification (2′-O-methyl) ++ 64%  1% 5-A CAGAAAGAGUUCGAGGAGTT (SEQ ID NO: 1246) TTUGU CUUUCUCAAGCUCCUC-5 (SEQ ID NO: 1247)

TABLE 169 527-545 BP Rat BIRC5(NM_022274) (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 169-1 Unmodified siRNA + 75% 0% 5-AGGAGACCGUGACAUUUCGTT (SEQ ID NO: 1248) TTUCCUCUGGCACUGUAAAGC-5 (SEQ ID NO: 1249) 169-2 Random modification (2′-deoxy-2′-fluoro) +++ 33% 24%  5-AGGAGACCGUGACAUUUCGTT (SEQ ID NO: 1250) TTUCCUCUGGCACUGUAAAGC-5 (SEQ ID NO: 1251) 169-3A Specific modification (2′-deoxy-2′-fluoro) +++ 69% 6% 5-AGGAGACCG UGA CAUUUCGTT (SEQ ID NO: 1252) TTUCCUCUGGC ACUGU AAAGC-5 (SEQ ID NO: 1253) 169-3B Specific modification (2′-deoxy-2′-fluoro) +++ 72% 3% 5-AGGAGACCG UGA C AUUUCGTT (SEQ ID NO: 1254) TTUCCUCUGGCACUGU AAAGC-5 (SEQ ID NO: 1255)

TABLE 170 42-60 BP Rat BIRC5(NM_022274) (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 170-1 Unmodified siRNA + 73% 0% 5-ACCUUAAGGACCACCGGAUTT (SEQ ID NO: 1256) TTUGGAAUUCCUGGUGGCCUA-5 (SEQ ID NO: 1257) 170-2 Random modification (2′-deoxy-2′-fluoro) ++ 41% 25%  5-ACCUUAAGGACCACCGGAUTT (SEQ ID NO: 1258) TTUGGAAUUCCUGGUGGCCUA-5 (SEQ ID NO: 1259) 170-3A Specific modification (2′-deoxy-2′-fluoro) ++ 70% 8% 5-ACCU UAAGGAC CA CCGGAUTT (SEQ ID NO: 1260) TTUGGA AU UCCUGGU GGCCUA-5 (SEQ ID NO: 1261) 170-3B Specific modification (2′-deoxy-2′-fluoro) ++ 71% 1% 5-ACCU UAAGGACCACCGGAUTT (SEQ ID NO: 1262) TTUGGAAUUCCUGGU GGCCUA-5 (SEQ ID NO: 1263)

TABLE 171 Rat BIRC5(NM_022274) 56-74 BP (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 171-1 Unmodified siRNA + 44% 0% 5-CGGAUCUACACCUUCAAGATT (SEQ ID NO: 1264) TTGCCUAGAUGUGGAAGUUCU-5 (SEQ ID NO: 1265) 171-2 Random modification (2′-O-methyl) ++ 29% 27%  5-CGGAUCUACACCUUCAAGATT (SEQ ID NO: 1266) TTGCCUAGAUGUGGAAGUUCU-5 (SEQ ID NO: 1267) 171-3A Specific modification (2′-O-methyl) ++ 40% 9% 5-CGGAUC UACACCUU CAAGATT (SEQ ID NO: 1268) TTGCCUAGAUGU GGAAGU UCU-5 (SEQ ID NO: 1269) 171-3B Specific modification (2′-O-methyl) ++ 42% 2% 5-CGGAUC UACACCUUCA AGATT (SEQ ID NO: 1270) TTGCCUAGAUGU GGAAGUUCU-5 (SEQ ID NO: 1271)

TABLE 172 Rat BIRC5(NM_022274) 183-201 BP (SEQ ID NO: 728) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 172-1 Unmodified siRNA + 77% 0% 5-GCUUUAAGGAACUGGAAGGTT (SEQ ID NO: 1272) TTCGAAAUUCCUUGACCUUCC-5 (SEQ ID NO: 1273) 172-2 Random modification (2′-O-methyl) ++ 51% 29%  5-GCUUUAAGGAACUGGAAGGTT (SEQ ID NO: 1274) TTCGAAAUUCCUUGACCUUCC-5 (SEQ ID NO: 1275) 172-3A Specific modification (2′-O-methyl) ++ 72% 8% 5-GCUU UA AGGAAC UGGAAGGTT (SEQ ID NO: 1276) TTCGAA AU UCCUUGAC CUUCC-5 (SEQ ID NO: 1277) 172-3B Specific modification (2′-O-methyl) ++ 74% 1% 5-GCUUUA AGGAAC UGGAAGGTT (SEQ ID NO: 1278) TTCGAAAUUCCUUGAC CUUCC-5 (SEQ ID NO: 1279)

TABLE 173 290-308 BP Mice (NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 173-1 Unmodified siRNA + 75% 0% 5-GAGAGAGACGGUGGAAGAATT (SEQ ID NO: 1280) TTCUCUCUCUGCCACCUUCUU-5 (SEQ ID NO: 1281) 173-2 Random modification (2′-O-methyl) +++ 56% 22%  5-GAGAGAGACGGUGGAAGAATT (SEQ ID NO: 1282) TTCUCUCUCUGCCACCUUCUU-5 (SEQ ID NO: 1283) 173-3A Specific modification (2′-O-methyl) +++ 72% 4% 5-GAGAGAGACGG UG GAAGAATT (SEQ ID NO: 1284) TTCUCUCUCUGCCAC CUUCUU-5 (SEQ ID NO: 1285) 173-3B Specific modification (2′-O-methyl) +++ 74% 1% 5-GAGAGAGACGGUGGAAGAATT (SEQ ID NO: 1280) TTCUCUCUCUGCC ACCUUCUU-5 (SEQ ID NO: 1286)

TABLE 174 791-809 BP Mice (NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 174-1 Unmodified siRNA + 53% 0% 5-AUCCUGCAGAAGAAGCCUCTT (SEQ ID NO: 1287) TTUAGGACGUCUUCUUCGGAG-5 (SEQ ID NO: 1288) 174-2 Random modification (2′-O-methyl) ++ 37% 24%  5-AUCCUGCAGAAGAAGCCUCTT (SEQ ID NO: 1289) TTUAGGACGUCUUCUUCGGAG-5 (SEQ ID NO: 1290) 174-3A Specific modification (2′-O-methyl) ++ 50% 6% 5-AUCC UGCAGAAGAAGCCUCTT (SEQ ID NO: 1291) TTUAGGACGU CUUCUUCGGAG-5 (SEQ ID NO: 1292) 174-3B Specific modification (2′-O-methyl) ++ 74% 1% 5-AUCC UGCAGAAGAAGCCUCTT (SEQ ID NO: 1293) TTUAGGACGUCUUCUUCGGAG-5 (SEQ ID NO: 1288)

TABLE 175 247-265 BP Mice (NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 175-1 Unmodified siRNA + 84% 0% 5-UCCUCGUCGUCUGUUCUAATT (SEQ ID NO: 1294) TTAGGAGCAGCAGACAAGAUU-5 (SEQ ID NO: 1295) 175-2 Random modification (2′-deoxy-2′-fluoro) ++ 49% 23%  5-UCCUCGUCGUCUGUUCUAATT (SEQ ID NO: 1296) TTAGGAGCAGCAGACAAGAUU-5 (SEQ ID NO: 1297) 175-3A Specific modification (2′-deoxy-2′-fluoro) ++ 77% 6% 5-UCCUCGUCGUC UG UUC UAATT (SEQ ID NO: 1298) TTAGGAGCAGCAGAC AAGAU U-5 (SEQ ID NO: 1299) 175-3B Specific modification (2′-deoxy-2′-fluoro) ++ 74% 1% 5-UCCUCGUCGUCUGUUC UAATT (SEQ ID NO: 1300) TTAGGAGCAGCAGAC AAGAU U-5 (SEQ ID NO: 1301)

TABLE 176 1148-1166 BP Mice (NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 176-1 Unmodified siRNA + 89% 0% 5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 1302) UUUUGGGUGGUGUCGAUCUUG-5 (SEQ ID NO: 1303) 176-2 Random modification (2′-deoxy-2′-fluoro) +++ 57% 21%  5-AACCCACCACAGCUAGAACUU (SEQ ID NO: 1304) UUUUGGGUGGUGUCGAUCUUG-5 (SEQ ID NO: 1305) 176-3A Specific modification (2′-deoxy-2′-fluoro) +++ 79% 9% 5-AACC CACCACAGC UAGAACUU (SEQ ID NO: 1306) UUUUGGGU GGUGU CGAU CUUG-5 (SEQ ID NO: 1307) 176-3B Specific modification (2′-deoxy-2′-fluoro) +++ 86% 1% 5-AACC CACCACAGC UAGAACUU (SEQ ID NO: 1308) UUUUGGGUGGUGU CG AU CUUG-5 (SEQ ID NO: 1309)

TABLE 177 3694-3712 BP Mice (NM_008960.2) (SEQ ID NO: 19) Locus Expression Growth gene SIRNA Stability inhibition ratio inhibition ratio 177-1 Unmodified siRNA + 77% 0% 5-UUACAAAGGAUCUCCUCCCTT (SEQ ID NO: 1310) TTAAUGUUUCCUAGAGGAGGG-5 (SEQ ID NO: 1311) 177-2 Random modification (2′-O-methyl) ++ 51% 29%  5-UUACAAAGGAUCUCCUCCCTT (SEQ ID NO: 1312) TTAAUGUUUCCUAGAGGAGGG-5 (SEQ ID NO: 1313) 177-3A Specific modification (2′-O-methyl) ++ 72% 6% 5-U UACAAAGGAUCUCCUCCCTT (SEQ ID NO: 1314) TTAAUGU UUCCUAGAGGAGGG-5 (SEQ ID NO: 1315) 177-3B Specific modification (2′-O-methyl) ++ 74% 1% 5-UUACAAAGGAUCUCCUCCCTT (SEQ ID NO: 1316) TTAAUGUUUCCUAGAGGAGGG-5 (SEQ ID NO: 1317)

TABLE 178 75-93 BP Aspergillus AF293 protein(XM_748400) Locus Expression Growth gene (SEQ ID NO: 851) SIRNA Stability inhibition ratio inhibition ratio 178-1 Unmodified siRNA + 58% 0% 5-AAACGAGAGAGCCCACCUUTT (SEQ ID NO: 1318) TTUUUGCUCUCUCGGGUGGAA-5 (SEQ ID NO: 1319) 178-2 Random modification (2′-O-methyl) +++ 37% 27%  5-AAACGAGAGAGCCCACCUUTT (SEQ ID NO: 1320) TTUUUGCUCUCUCGGGUGGAA-5 (SEQ ID NO: 1321) 178-3A Specific modification (2′-O-methyl) +++ 56% 4% 5-AAACGAGAGAGCC CACCUUTT (SEQ ID NO: 1322) TTUUUGCUCUCUCGG GU GGAA-5 (SEQ ID NO: 1323) 178-3B Specific modification (2′-O-methyl) +++ 57% 1% 5-AAACGAGAGAGCCCACCUUTT (SEQ ID NO: 1318) TTUUUGCUCUCUCGGGU GGAA-5 (SEQ ID NO: 1324)

TABLE 179 137-155 BP Aspergillus AF293 protein(XM_748400) Locus Expression Growth gene (SEQ ID NO: 851) SIRNA Stability inhibition ratio inhibition ratio 179-1 Unmodified siRNA + 69%  0% 5-AAAGCGGUGGAUCAGCUCUTT (SEQ ID NO: 1325) TTUUUCGCCACCUAGUCGAGA-5 (SEQ ID NO: 1326) 179-2 Random modification (2′-O-methyl) ++ 43% 24% 5-AAAGCGGUGGAUCAGCUCUTT (SEQ ID NO: 1327) TTUUUCGCCACCUAGUCGAGA-5 (SEQ ID NO: 1328) 179-3A Specific modification (2′-O-methyl) ++ 63% 10% 5-AAAGCGG UG GAU CAGCUCUTT (SEQ ID NO: 1329) TTUUUCGCC AC CUAGU CGAGA-5 (SEQ ID NO: 1330) 179-3B Specific modification (2′-O-methyl) ++ 67%  1% 5-AAAGCGGUGGAUCAGCUCUTT (SEQ ID NO: 1325) TTUUUCGCCAC CUAGU CGAGA-5 (SEQ ID NO: 1331)

TABLE 180 360-378 BP Aspergillus AF293 protein(XM_748400) Locus Expression Growth gene (SEQ ID NO: 851) SIRNA Stability inhibition ratio inhibition ratio 180-1 Unmodified siRNA + 71% 0% 5-UCCAAGCUUCCUCGUUGGUTT (SEQ ID NO: 1332) TTAGGUUCGAAGGAGCAACCA-5 (SEQ ID NO: 1333) 180-2 Random modification (2′-deoxy-2′-fluoro) ++ 51% 28%  5-UCCAAGCUUCCUCGUUGGUTT (SEQ ID NO: 1334) TTAGGUUCGAAGGAGCAACCA-5 (SEQ ID NO: 1335) 180-3A Specific modification (2′-deoxy-2′-fluoro) ++ 65% 7% 5-UC CAAGCUUCCUCGU UG GUTT (SEQ ID NO: 1336) TTAGGU UCGAAGGAGCA AC CA-5 (SEQ ID NO: 1337) 180-3B Specific modification (2′-deoxy-2′-fluoro) ++ 71% 0% 5-UCCAAGCUUCCUCGUUGGUTT (SEQ ID NO: 1332) TTAGGU UCGAAGGAGCAAC CA-5 (SEQ ID NO: 1338)

TABLE 181 14-32 BP Aspergillus AF293 protein (XM_748400) Locus Expression Growth gene (SEQ ID NO: 851) SIRNA Stability inhibition ratio inhibition ratio 181-1 Unmodified siRNA + 90% 0% 5-AGAGAGGUGGAGGUAUCUCTT (SEQ ID NO: 1339) TTUCUCUCCACCUCCAUAGAG-5 (SEQ ID NO: 1340) 181-2 Random modification (2′-deoxy-2′-fluoro) +++ 68% 26%  5-AGAGAGGUGGAGGUAUCUCTT (SEQ ID NO: 1341) TTUCUCUCCACCUCCAUAGAG-5 (SEQ ID NO: 1342) 181-3A Specific modification (2′-deoxy-2′-fluoro) +++ 85% 7% 5-AGAGAGG UGGAGG UAUCUCTT (SEQ ID NO: 1353) TTUCUCUCC AC CUCCAU AGAG-5 (SEQ ID NO: 1354) 181-3B Specific modification (2′-deoxy-2′-fluoro) +++ 88% 1% 5-AGAGAGG UGGAGGUAUCUCTT (SEQ ID NO: 1343) TTUCUCUCCACCUCCAU AGAG-5 (SEQ ID NO: 1344)

TABLE 182 1238-1256 BP Aspergillus AF293 protein(XM_748400) Locus Expression Growth gene (SEQ ID NO: 851) SIRNA Stability inhibition ratio inhibition ratio 182-1 Unmodified siRNA + 73% 0% 5-CCGAAGACGAAGCUAUGAATT (SEQ ID NO: 1345) TTGGCUUCUGCUUCGAUACUU-5 (SEQ ID NO: 1346) 182-2 Random modification (2′-O-methyl) +++ 51% 29%  5-CCGAAGACGAAGCUAUGAATT (SEQ ID NO: 929) TTGGCUUCUGCUUCGAUACUU-5 (SEQ ID NO: 930) 182-3A Specific modification (2′-O-methyl) +++ 69% 6% 5-CCGAAGACGAAGC UAUGAATT (SEQ ID NO: 1355) TTGGCUUCUGCUUCGAUAC UU-5 (SEQ ID NO: 932) 182-3B Specific modification (2′-O-methyl) +++ 71% 1% 5-CCGAAGACGAAGC UAUGAATT (SEQ ID NO: 1347) TTGGCUUCUGCUUCGAUAC UU-5 (SEQ ID NO: 1348) In tables 1-182: Chemically modified nucleotides were indicated by bold letters of “A”, “U”, “G” or “C”; “+” indicates the situation that after serum treatment, the main siRNA band disappeared completely, while evident siRNA degradation bands were observed; “++” indicates the situation that after serum treatment, the main siRNA band remains visible although degradation occurs, at the same time, siRNA degradation bands are easily observed; “+++” indicates the situation that after serum treatment, no obvious degradation occurs with the main siRNA band, no siRNA degradation band is observed.

In addition, as shown in table 1-182, the specific siRNA modification strategy provided by the present invention greatly improves serum stability of the siRNAs; while at the same time, reduces their cytotoxicity and does not compromise their gene silencing activity. Thus, the present invention can achieve siRNA stabilization with minimal chemical modifications, decreases their potential cytotoxicity and influence on gene silencing activity. 

The invention claimed is:
 1. A modified oligonucleotide comprising a first nucleic acid fragment and a second nucleic acid fragment, wherein each of said first nucleic acid fragment and said second nucleic acid fragment is 18 to 30 nucleotides in length; said first nucleic acid fragment and said second nucleic acid fragment can form double-stranded region; said first nucleic acid fragment contains at least one contiguous CA or UG sequence, said second nucleic acid fragment contains at least one contiguous CA or UG sequence complementary to the CA or UG sequence in said first nucleic acid fragment, the CA or UG sequence(s) of said first nucleic acid fragment and the CA or UG sequence(s) of said second nucleic acid fragment pair to form CA/UG and/or UG/CA site(s); wherein at least one of the nucleotides in at least one of the CA/UG and/or UG/CA site(s) is a modified nucleotide; wherein all other nucleotides are unmodified nucleotides; and said modified nucleotide(s) providing improved stability of said modified oligonucleotide in mammalian serum compared to stability of an unmodified oligonucleotide.
 2. The modified oligonucleotide of claim 1, wherein said oligonucleotide contains at least one CA/UG and/or UG/CA site(s).
 3. The modified oligonucleotide of claim 1, wherein only cytidine nucleotide(s) in all occurrences of the CA/UG or UG/CA site is/are modified nucleotide(s).
 4. The modified oligonucleotide of claim 1, wherein only one cytidine nucleotide in the CA/UG or UG/CA site(s) is modified nucleotide.
 5. The modified oligonucleotide of claim 1, wherein the first nucleic acid fragment and the second nucleic acid fragment are in two separate nucleic acid strands or in a single nucleic acid strand.
 6. The modified oligonucleotide of claim 1, wherein the modified oligonucleotide is a hairpin-structured and single-stranded nucleic acid molecule, the complementary nucleic acid sequences of the first nucleic acid fragment and the second nucleic acid fragment pair to form double-stranded region.
 7. The modified oligonucleotide of claim 5, wherein the modified oligonucleotide contains a sense strand and an antisense strand, the sense strand and the antisense strand are contiguous nucleic acid fragments; the first nucleic acid fragment is in the sense strand, and the second nucleic acid fragment is in the antisense strand.
 8. The modified oligonucleotide of claim 5, wherein the modified oligonucleotide contains a sense strand and an antisense strand, the sense strand contains two or more discontiguous sense-strand component fragments, the antisense strand is a contiguous nucleic acid fragment; the first nucleic acid fragment is in one or more sense-strand component fragments, the second nucleic acid fragment is in the antisense strand.
 9. The modified oligonucleotide of claim 1, wherein the modified oligonucleotide is a hybrid nucleic acid molecule comprising ribonucleotides and at least one deoxyribonucleotide.
 10. The modified oligonucleotide of claim 1, wherein the modified oligonucleotide has at least one of the following modifications: (a) modifying the phosphodiester bond(s) connecting nucleotides in the oligonucleotide; (b) modifying the sugar(s) of the nucleotide in the oligonucleotide; (c) modifying the base(s) of the nucleotide in the oligonucleotide.
 11. The modified oligonucleotide of claim 10, wherein the modification is replacing a 2′-OH group on the sugar with a 2′-modified nucleotide.
 12. The modified oligonucleotide of claim 11, wherein the modification is replacing a 2′-OH group on the sugar with a 2′-O-methyl group or a 2′-deoxy-2′-fluoro group.
 13. A pharmaceutical composition for inhibiting the expression of a target gene in a mammal, wherein the pharmaceutical composition comprises at least one modified oligonucleotide of claim 1, and a pharmaceutically acceptable carrier.
 14. A method for preparing the pharmaceutical composition of claim 13 comprising formulating the oligonucleotide of claim 1 and a pharmaceutically acceptable carrier.
 15. A method for inhibiting the expression of a target gene in a cell, comprising: (a) introducing the oligonucleotide of claim 1 into the cell; and (b) incubating the cell for a time sufficient to obtain inhibition of the expression of the target gene in the cell.
 16. The method of claim 15, wherein the cell is a mammalian cell.
 17. A method for preparing an oligonucleotide that is highly stable in a biological sample and can inhibit the expression of a target gene, comprising: (a) selecting one or more nucleic acid sequences of between 18 and 30 nucleotides in length from the nucleotide sequence of the mRNA resulting from the transcription of the target gene; and (b) synthesizing the selected sequences, wherein one strand comprises a sequence complementary to selected sequence in (a); and (c) testing one or more oligonucleotides of (b) for their activity to inhibit the expression of the target gene in a biological sample; and (d) selecting one or more oligonucleotides of (c) possessing the activity to inhibit the expression of the target gene in a biological sample; and (e) in the oligonucleotides selected in (d), identifying in the nucleotide sequences of all occurrences of the CA/UG and UG/CA site(s); and (f) synthesizing one or more oligonucleotides selected in (d), wherein at least one nucleotide in the CA/UG and UG/CA site(s) identified in (e) is replaced by a corresponding modified nucleotide; wherein only cytidine nucleotide(s) in all occurrences of the CA/UG or UG/CA site is/are modified, and wherein all the nucleotides are unmodified nucleotides except the nucleotides in said CA/UG and/or UG/CA site(s).
 18. A method of inhibiting expression of a target gene in a subject, said method comprises administering to a said subject a pharmaceutical composition comprising the oligonucleotide of claim 1 and a pharmaceutically acceptable carrier, wherein the target gene is sufficiently complementary to hybridize to the oligonucleotide of claim 1 and inhibit expression.
 19. The method of claim 18, wherein the subject is a human being.
 20. A method for preparing an oligonucleotide with nuclease resistance, said method comprising the steps of: (a) identifying in the nucleotide sequence of the oligonucleotide all occurrences of CA/UG and UG/CA site(s); and (b) synthesizing the oligonucleotide, wherein at least one nucleotide in the CA/UG and UG/CA site(s) identified in (a) is replaced by a modified corresponding nucleotide; wherein only cytidine nucleotide(s) in all occurrences of CA/UG or UG/CA site is/are modified, and wherein all the nucleotides are unmodified nucleotides except the nucleotides in said CA/UG and/or UG/CA site(s).
 21. A method to identify an oligonucleotide with stability in biological samples, comprising the steps of: (a) providing a first modified oligonucleotide of claim 1, and a second oligonucleotide identical in sequence to the first oligonucleotide except that it does not have modified nucleotide(s) of the oligonucleotide of claim 1; and (b) determining the stability and the degradation process of said first and second oligonucleotide in a biological sample by contacting the two oligonucleotides with the biological sample under identical conditions, whereby, where the first modified oligonucleotide is degraded less rapidly than the second oligonucleotide, an oligonucleotide with stability in a biological sample is identified.
 22. The modified oligonucleotide of claim 1, wherein the first nucleic acid fragment contains at least one contiguous UA sequence and at least one contiguous CA or UG sequence, the second nucleic acid fragment contains at least one contiguous UA sequence complementary to the UA sequence of the first nucleic acid fragment and one contiguous CA or UG sequence complementary to the CA or UG sequence of the first nucleic acid fragment, the UA sequence(s) of the first nucleic acid fragment and the UA sequence(s) of the second nucleic acid fragment pair to form UA/UA site(s), the CA or UG sequence(s) of the first nucleic acid fragment and the UG or CA sequence(s) of the second nucleic acid fragment pair to form CA/UG or UG/CA site(s); wherein at least one of the nucleotides in at least one of the UA/UA site(s) is a modified nucleotide, and at least one of the nucleotides in at least one of the CA/UG or UG/CA site(s) is a modified nucleotide.
 23. The modified oligonucleotide of claim 22, wherein at least one uridine nucleotide in the UG/CA site(s) is modified nucleotide. 